Condensation of 1 with active methylene and different amino pyrazoles produced the respective Schiff bases 2–4, 8 and 9. On the other hand, 1 was reacted with ethyl cyanoacetate and thiourea in one-pot reaction to afford the pyrazolo-6- thioxopyridin-2-[3H]-one (10). Moreover, α–β unsaturated chalcone derivative 11 was prepared via the reaction of compound 1 with P-methoxy acetophenone, which in turn reacted with each of ethyl cyanoacetate, malononitrile, hydrazine hydrate, and thiosemicarbazide to afford the corresponding pyridine and pyrazole derivatives 13, 14, 17, and 20. The structure of newly synthesized compounds was characterized by analytical and spectroscopic data . All new compounds were evaluated against 5α-reductase and aromatase inhibitors and the results showed that many of these compounds inhibit 5α-reductase and aromatase activity; compound 13 was found to be the highest potency among the tested samples comparing with the reference drugs.This work describes the utility of pyrazole-4-carbaldehyde  The pharmaceutical importance of 1,2,3-triazole ring is due to its efficacy as c-Met kinase inhibitors , antiproOn the other hand, pyrazoline derivatives are a very important class of heterocyclic compounds characterized by biological activities as antiviral , antican1 , which agrees with its molecular formula C22H15N7.It has been found that the reaction of pyrazole . As an example, structure 6 was supported by its mass spectrum (m/z 407) [M+], which agrees with its molecular formula C24H21N7. Its IR spectrum (KBr/cm−1) showed an absorption band at v 1600 cm−1, which corresponds to the C=C, a band at v 1620 cm−1 due to C=N, and a band at v 2862, 2924 cm−1ue to CH-aliphatic. Its 1H-NMR spectrum displayed four singlet signals at δ = 2.53, 2.75, 6.37, and 8.35 ppm. due to two -CH3, CH-pyrazole and CH-olefinic, respectively, one multiple signal at δ = 7.35–7.84 ppm. related to the 10 protons of aromatic. he other bands of compounds 5 and 7 appeared in IR, 1H-NMR spectra and molecular weight determination (MS) in the expected regions.The newly synthesized Schiff bases derivatives ectively . The str1 was allowed to react with each of 4-cyano-3-aminopyrazole and 5-phenyl-3-aminopyrazole in boiling glacial acetic acid via Schiff-base to afford the corresponding 8 and 9 respectively in a good yield  [M+], which agrees with its molecular formula C23H17N9. Its IR spectrum (KBr/cm−1) revealed a strong absorption band at v 2222 cm−1 due to C≡N and a strong absorption band at v 3105 cm−1 attributed to the NH group. 1H-NMR spectrum of compounds 8 and 9 revealed a proton at δ = 8.50 and 8.51 ppm. which was assigned to the appearance of the CH-olefinic of Schiff-base. The other bands of compounds 8 and 9 appeared in IR, 1H-NMR spectra and molecular weight determination (MS) in the expected regions.Compound od yield . The str1 with ethyl cyanoacetate and thiourea in the presence of hydrochloric acid in refluxing ethanol afforded the corresponding derivative 10 through the mechanism illustrated in (10. Structure 10 was supported by its mass spectrum (m/z 454) [M+], which agrees with its molecular formula C23H18N8OS. Its IR spectrum (KBr/cm−1) showed a strong absorption band at v 1400 cm−1, which is attributed to C=S, a strong absorption band at v 3228 cm−1 due to (NH) and a strong absorption forked band at v 3317, 3348 cm−1due to the NH2 group. Its 1H-NMR spectrum displayed five singlets at δ = 2.53, 6.31, 6.82, 8.21, and 9.50 ppm. due to CH3, CH-pyrazole, NH2group, CH-olefinic, and NH protons, respectively, and one multiple at δ = 7.35-7.84 ppm. related to the 10 protons of aromatic.It has now been found that one-pot reaction of compound rated in . The rea1 reacted with P-methoxy acetophenone to give the α–β unsaturated derivative 1-(4-methoxyphenyl)-3--1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one 11 , elemental analysis and chemical transformation. However, the structure of 11 was inferred chemically via its interaction with each of ethyl cyanoacetate and malononitrile to give the corresponding 13 and 14 respectively  and correct elemental analysis. The IR spectrum of compound 13 showed a strong absorption band at v 3066, 3133 cm−1 attributed to the NH2 group, and a strong absorption band at v 1740 cm−1attributed to the carbonyl ester and devoid of any band for the C≡N group. Its 1H-NMR exhibited a triple signal at δ = 1.02–1.21 ppm attributed to the three protons of the CH3 group of ethyl ester and as a quartet signal δ at 3.90–4.12 ppm attributed to the two protons of the CH2 group of ethyl ester, which confirmed the formation of compounds 13 and not 12.The structure of chalcone ectively . The str14 showed a strong sharp absorption band at 2212 cm−1 represented the C≡N which indicated the formation of compound 14. he other bands of compounds 13 and 14 appeared in IR, 1H-NMR spectra molecular weight determination (MS) in the expected regions.On the other hand, the IR spectrum of compound 11 was allowed to react with hydrazine hydrate it yielded the corresponding substituted pyrazole 17 in a good yield through the reasonable mechanism discussed in , elemental analysis and chemical transformation. The bands of compounds 17 appeared in IR, 1H-NMR spectra molecular weight determination (MS) in the expected regions.When the chalcone ussed in . The rea11 with thiosemicarbazide gave pyrazoline derivative 20 as shown in 18 results from 1,2-addition of thiosemicarbazide to the carbonyl group of chalcone 11 and subsequent N-H intermolecular cycloaddition to the double bond of 18, which leads to the formation of 20. As a result and in accordance with the currently accepted mechanism , which agrees with its molecular formula C23H18N8OS. Its IR spectrum (KBr/cm−1) showed an absorption band at v 3475, 3436 cm−1due to NH2, a band at v 2924, 2890 cm−1 due to CH-alphatic, a band at v 1562 cm−1 due to C=C and a due to v1616 cm−1 due to C=N Its 1H-NMR spectrum displayed three singlet signals at δ = 2.54, 3.11 and 4.61 ppm due to CH3, OCH3-NH2 group protons respectively, one doublet at δ = 3.40-3. 47 related to CH2-pyrazole, and two multiples at δ = 3.74–3.82 and 7.01–7.72 ppm. related to CH2 protons and 15 protons of aromatic.Finally, condensation of chalcone echanism , the fortomerism  may take1–11, 13, 14, 17, and 20 were screened for their 5α-reductase inhibitor activity in vivo. All the tested compounds showed 5α-reductase inhibitor activities with good 50IC (µM); compounds  indicated a significant activity compared to the control drug anastrozole. IC50 values were determined. From the results, it is evident that 12 of the investigated compounds have displayed a potent activity as a 5α-Reductase inhibitor , which may increase their reactivity either.Circulating testosterone and dihydrotestosterone hormone levels or tissue concentrations were measured after the administration of 5α-reductase inhibitor radioimmuno assays. All new synthesized compounds nhibitor ; the pot1–11, 13, 14, 17, and 20 were tested for their aromatase inhibitor activity in vivo. From the results given in 7–11, 13, 14, 17, and 20) have given a potent activity as aromatase inhibitors compared to the standard drug letrozole. Compound 13 was found to be the most potent aromatase inhibitor compared to the tested compounds, and the standard drug Letrazole may be due to the presence of the ester group and pyridine ring. Compound 8 showed high activity, which may be due to the presence of the cyano group; also, compound 11 showing high activity may be due to the presence of α-β unsaturated ketone; compound 20 showing high reactivity may be due to the thioamide group; and compound 17 showing high activity may be due to the pyrazoline ring system. In addition, compound 14 may have showed high activity due to the cyano-pyridine ring system. Compound 7 showing high activity may be due to the presence of pyrazole and pyrazolone ring systems, and compound 10 showing high reactivity may be due to the presence of the thioprymidone ring system. Also, the reactivity of compound 9 may be due to the presence of the pyrazole ring system. This is all in addition to their physical properties , which may increase their reactivity.All synthesized compounds 1-NMR spectra were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini 400 MHz spectrometer, and chemical shifts are expressed in δ ppm units using TMS as an internal reference. Mass spectra were recorded on a GC-MS QP1000 EX Shimadzu. Elemental analyses were carried out at the Microanalytical Center of Cairo University.All melting points were determined on an electrothermal apparatus and are uncorrected. IR spectra were recorded (KBr discs) on a Shimadzu FT-IR 8201 PC spectrophotometer. H1 [2–4, respectively, in a good yield.A mixture of 1  : Yellow crystals from acetic acid in yield 93%, m.p. 200–202 °C. H1-NMR : δ = 2.52 , 6.37 , 8.34 , 7.33–7.94 . IR : v 1620 (C=C), 1640 (C=N), 2222 v (CN), 2854, 2927 . MS m/z , , . Anal. Calcd. for C22H15N7 (377): C, 70.01; H, 4.01; N, 25.98; Found: C, 70.09; H, 4.08; N, 25.90%.2--1-phenyl-1H-pyrazol-4-yl)methylene)malononitrile (3): Pale yellow crystals from acetic acid in yield 81%, m.p. 222–224 °C. H1-NMR : δ = 2.39 , 2.52 , 6.33 , 8.34 , 7.37–7.94 . IR : v 1620 (C=C), 1639 (C=N), 1693 (C=O), 2927, 2974 ; MS m/z , , . Anal. Calcd. for C24H21N5O2 (411): C, 70.06; H, 5.14; N, 17.02; Found: C, 70.01; H, 5.10; N, 17.09%.3--1-phenyl-1H-pyrazol-4-yl)methylene)pentane-2,4-dione (4): White crystals from ethanol in yield 87%, m.p. 210–212 °C. H1-NMR : δ = 1.24–129 , 2.53, 4.16–4.23 , 6.38 , 8.33 , 7.35–7.84 . IR : v 1620 (C=C), 1632 (C=N), 1697 (C=O), 2862, 2927 . MS: m/z , , . Anal. Calcd. for C26H25N5O4 (471): C, 66.23; H, 5.34; N, 14.85; Found: C, 66.14; H, 5.25; N, 14.89%.Diethyl2--1-phenyl-1H-pyrazol-4-yl)methylene) malonate  and hydrazine hydrate  was heated under reflux in absolute ethanol (20 mL) for (3 h); the reaction mixture was cooled, and the solid formed was collected and recrystallized to afford the corresponding derivatives 5, 6 and 7, respectively.A mixture of the appropriate of compounds 5): White crystals from ethanol in yield 78%, m.p. 240–242 °C. H1-NMR : δ = 2.53 , 5.70 , 6.39 , 8.33 , 7.35–7.84 . IR : v 1608 (C=C), 1626 (C=N), 2862, 2927 , 3310, 3244 (NH2); MS: m/z , , . Anal. Calcd. for C22H19N9 (409): C, 64.53; H, 4.68; N, 30.79; Found: C, 64.38; H, 4.55; N, 30.65%.4--1-phenyl-1H-pyrazol-4-yl)methylene)-4H-pyrazole-3,5-diamine (6): White crystals from ethanol in yield 87%, m.p. 261–263 °C. H1-NMR : δ = 2.53 , 2.75 , 6.37 , 8.35 , 7.35–7.84 . IR : v 1600 (C=C), 1620 (C=N), 2862, 2924  MS: m/z , , . Anal. Calcd. for C24H21N7 (407): C, 70.74; H, 5.19; N, 24.06; Found: C, 70.55; H, 5.11; N, 23.95%.5-methyl-4-methyl)-1-phenyl-1H-pyrazol-3-yl)-1-phenyl-1H-1,2,3-triazole (7): Grey crystals from ethanol in yield 82%, m.p. 282–284 °C. H1-NMR : δ = 2.53 , 6.67 , 8.35 , 7.35–7.84 , 11.00 . IR : v 1600 (C=C), 1620 (C=N), 1640 (C=O), 2862, 2924 , 3236 (NH). MS: m/z , , . Anal. Calcd. for C22H17N7O2 (411): C, 64.23; H, 4.16; N, 23.83; Found: C, 64.32; H, 4.09; N, 23.92%.4--1-phenyl-1H-pyrazol-4-yl)methylene) pyrazolidine-3,5-dione  and the appropriate amount of 3-amino-4-cyano-1H-pyrazole and 3-amino-5-phenyl-1H-pyrazole was heated under reflux in acetic acid for 2 h. The solid formed through heating was separated and recrystallized from the appropriate solvent to give the corresponding compounds 8 and 9, respectively.A mixture of compound number 8): Orange crystals from Dioxane in yield 91%, m.p. 161–163 °C. H1-NMR : δ = 2.53 , 6.32 , 6.67 , 7.35–7.84 , 8.50 , 9.11 . IR : v 1600v (C=C), 1616 (C=N), 2222 (CN), 2858, 2974 , 3105 (NH). MS: m/z , , . Anal. Calcd. for C23H17N9 (419): C, 65.86; H, 4.09; N, 30.05; Found: C, 65.92; H, 4.03; N, 30.01%.5--1-phenyl-1H-pyrazol-4-yl)methyleneamino)-1H-pyrazole-4-carbonitrile (9): Beige crystals from Dioxane in yield 85%, m.p. 140–142 °C. H1-NMR : δ = 2.53 , 6.31 , 6.68 , 7.15–7.54 , 8.51 , 9.11 . IR : v 1600 (C=C), 1616 (C=N), 2858, 2984 , 3109 (NH). MS: m/z , , . Anal. Calcd. for C28H22N8 (470): C, 71.47; H, 4.71; N, 23.81; Found: C, 71.46; H, 4.72; N, 23.82%.N--1-phenyl-1H-pyrazol-4-yl)methylene)-3-phenyl-1H-pyrazol-5-amine (10): A mixture of compound number 1 , ethylcyanoacetate (10 mmol) and thiourea (10 mmol) was heated under reflux in absolute ethanol (20 mL) containing a catalytic amount of hydrochloric acid (1 mL) for (15 h); the solid formed while heating was separated and recrystallized from dioxane as yellow crystals in 87% yield. m.p. 230–232 °C. H1-NMR : δ = 2.53 , 6.31 , 6.82 , 7.5–7.8 , 8.21 , 9.50 . IR : v 1400 (C=S), 1600 (C=C), 1620 (C=N), 1639 (C=O), 2852, 2984 , 3228 (NH), 3317, 3348 (NH2). MS: m/z , , . Anal. Calcd. for C23H18N8OS (454): C, 60.78; H, 3.99; N, 24.65; Found: C, 60.76; H, 3.98; N, 24.64%.4-amino-1,6-dihydro-3--1-phenyl-1H-pyrazol-4-yl)methylene)-6-thioxopyridin-2(3H)-one (11): Sodium hydroxide  was added dropwise to a mixture of compound number 3  and p-methoxy acetophenone (10 mmol) in ethanol (20 mL) while stirring at 0–5 °C. The stirring was continued for 2 h. The resulting solid was collected and recrystallized from ethanol to give compound number 11 as white crystals in 94% yield. m.p. 168–170 °C. H1-NMR : δ = 2.53 , 3.11 , 6.51 , 7.3–7.69 , 796–7.99 . IR : v 1662 (C=O), 2842, 2921 . MS: m/z , , . Anal. Calcd. for C28H23N5O2 (461): C, 72.87; H, 5.02; N, 15.17; Found: C, 72.81; H, 5.06; N, 15.13%.1-(4-methoxyphenyl)-3--1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one (A: a mixture of the compound 11 (10 mmol) and the appropriate amount of ethyl cyanoacetate or malononitrile (10 mmol) and ammonium acetate  was heated under reflux in acetic acid (20 mL) for 5 h. On cooling, the separated solid was filtrated, washed with water and recrystallized from the proper solvent to give the corresponding compounds 13 and 14 respectively in a good yield.Method B: A mixture of the compound 1 (10 mmol), p-methoxy acetophenone (10 mmol), the appropriate amount of ethyl cyanoacetate or malononitrile (10 mmol), and an excess amount of ammonium acetate (4 gm) was heated under reflux in n-butanol (20 mL) for 3 h. On cooling, the separated solid was filtrated, washed with water and recrystallized from the proper solvent to give compounds identical in all aspects  with that obtained from method A.Method 13): Yellow crystals from ethanol in yield 73%, m.p. 250–252 °C. H1-NMR : δ = 1.02–1.21 , 2.53 , 3.11 , 3.90–4.12 , 6.34 , 7.07–7.67 , 6.15 , 8.50 . IR : v 1590 (C=C), 1601 (C=N), 1740 (C=O), 3066, 3133 (NH2). MS: m/z , . Anal. Calcd. for C33H29N7O3 (571): C, 69.34; H, 5.11; N,17.15; Found: C, 69.28; H, 5.03; N, 17.10%.Ethyl 2-amino-6-(4-methoxyphenyl)-4--1-phenyl-1H-pyrazol-4-yl)pyridine-3-carboxylate (14): Yellow crystals from ethanol in yield 71%, m.p. 271–273 °C. H1-NMR : δ = 2.53 , 3.11 , 6.11 , 6.34 , 7.37–8.10 , 8.50 . IR : v 1592 (C=C), 1610 (C=N), 2212 (CN), 3350, 3417 (NH2). MS: m/z . Anal. Calcd. for C31H24N8O (524): C, 70.98; H, 4.16; N, 21.36; Found: C,70.91; H, 4.12; N, 21.25%.2-Amino-6-(4-methoxyphenyl)-4--1-phenyl-1H-pyrazol-4-yl)pyridine-3-carbonitrile (17): A mixture of compound number 11 (5 mmol) and hydrazine hydrate  was heated under reflux in ethanol (10 mL) for 3 h. The reaction mixture was cooled and the resulting solid collected and recrystallized from ethanol as white crystals in yield 76%. Yellow crystals from ethanol in yield 71%, m.p. 291–293 °C. H1-NMR : δ = 2.53 , 3.11 , 3.44 , 3.89 , 4.99 , 6.34 , 7.07–7.66 . IR : v 1597 (C=C), 1620 (C=N), 3311 (NH). MS: m/z , . Anal. Calcd. for C28H25N7O (475): C,70.72; H, 5.30; N, 20.62; Found: C,70.72; H,5.29; N,20.61%.4--1H-pyrazol-5-yl)-1-phenyl-1H-pyrazol-3-yl)-5-methyl-1-phenyl-1H-1,2,3-triazole (20): A mixture of 1-(4-methoxyphenyl)-3--1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one 11. , thiosemicarbazide  in ethanol (20 mL) containing a catalytic amount of hydrochloric acid (0.5 mL) was heated under reflux for 3 h. The resulting solid was collected and recrystallized from dioxane to give 20 as white crystals in Yield: 82%, m.p. 207–209 °C. H1-NMR : δ = 2.54 , 3.11  3.40–3.47 , 3.74–3.82 , 4.61 , 7.01–7.72 . IR : v 3475, 3436 (NH2), 2924, 2890 , 1562 (C=C), 1616 (C=N). MS: m/z , , . Anal. Calcd. for C29H26N8OS (534): C, 65.15; H, 4.90; N, 20.69; Found: C, 65.14; H, 4.91; N, 20.69%.4,5-Dihydro-3-(4-methoxyphenyl)-5--1-phenyl-1H-pyrazol-4-yl)pyrazole-1-carbothioamide . The tested compounds were suspended in 5% Tween 80 in water. The vehicle was used for both the standard and negative control group, beginning on the postnatal 3rd day until the age of 7 weeks. Eighteen Groups were used to test the activities, of which one was used as the positive control for anastrozole and another served as the negative control group. After scarifying, blood was withdrawn for testosterone and dihydrotestosterone (DHT) determination . Moreoveex = 409 nm, λem = 530 nm) in a NADPH-regenerating system. Briefly, concentrated stock solutions of test compounds were prepared in acetonitrile.Inhibitory potencies of compounds were determined according to an established procedure using a commercially available aromatase test kit from BD Gentest . This fl+; 825 µM MgCl2; 825 µM glucose -6-phosphate; 50 µM citrate buffer, pH 7.5) were prepared in a 96-well plate. After incubating the plate for 10 min at 37 °C, 100 µL of an aromatase/P450 reductase/substrate solution  were added to each well. The plate was covered and incubated for 30 min at 37 °C. Seventy-five microliters of 0.5 M Tris base were then added to stop the reaction, and the fluorescence of the formed de-methylated MFC was measured with a plate reader .One-hundred microliter samples containing serial dilutions of test compounds (dilution factor of 3 between samples) and cofactor mixture (0.4 U/mL glucose-6-phosphate dehydrogenase; 16.2 µM NADP50 value, the inhibitor concentration necessary to reduce the enzyme activity by half. Each experiment was performed at least in triplicate.Fluorescence intensities, which were proportional to the amount of reaction product generated by aromatase, were graphed as a function of inhibitor concentration and then fit to a three-parameter logistic function. Inhibitory potencies were expressed in terms of the IC1 reacts with different active methylene and amino pyrazoles to yield a new series of pyrazole derivatives derived from 1,2,3-triazole derivative. Newly synthesized compounds 1–11, 13, 14, 17, and 20 were evaluated in vivo as 5α-reductase and aromatase inhibitors; most of the tested compounds exhibited more potent activity than the standard references drugs. Compound 13 has the highest potency amongst the tested compounds and the reference drugs, and this may be due to the presence of the pyridine moiety linked with pyrazoline and 1,2,3-trizole moieties. The combination between 1,2,3-triazole and pyrazole was found to be essential for 5α-reductase and aromatase inhibitor activities. Future work will involve the design of steroidal molecules of such features.Results of the present study demonstrate that compound


N-methylpyridyl (pyridinium) porphyrin family. PACT tests conducted with the tetracationic porphyrins of these three families showed that these new photosensitizers may offer a good alternative to the classical pyridinium porphyrins, especially against S.aureus and E.coli. In addition, they pave the way to new cationic photosensitizers by the means of derivatization through amide bond formation.Despite advances achieved over the last decade, infections caused by multi-drug-resistant bacterial strains are increasingly becoming important societal issues that need to be addressed. New approaches have already been developed in order to overcome this problem. Photodynamic antimicrobial chemotherapy (PACT) could provide an alternative to fight infectious bacteria. Many studies have highlighted the value of cationic photosensitizers in order to improve this approach. This study reports the synthesis and the characterization of cationic porphyrins derived from methylimidazolium and phenylimidazolium porphyrins, along with a comparison of their photophysical properties with the well-known  Since the introduction of penicillin in the 1940s, the era of antibiotics has been considered as miraculous, given that these treatments had significantly decreased the number of deaths resulting from bacterial infections . In addi3O2). Under appropriate light irradiation, PS activation leads to the production of singlet oxygen (1O2) by energy transfer, or oxygen radicals  by electron transfer. These reactive oxygen species (ROS) are able to rapidly react with a large panel of molecules  and cause cellular damages, which ultimately lead to cell death. The number and diversity of the cellular targets greatly limit the rise in bacterial strains that resist this treatment : calcd [M + 2H]2+ 310.11, found 310.31.3a (tetrakis(4-imidazol-phenyl)porphyrin):1H NMR : δ (ppm) = 8.92 , 8.36 , 8.26 , 7.86 , 7.67 , 7.34 ; MS (ESI+) [C56H38N12]: calcd [M + 2H]2+ 440.16, found 440.04.N-methylimidazol-2-yl)porphyrin):5a : δ (ppm) = 8.88 , 7.67 , 7.65 , 7.51 , 7.50 , 3.45 ; MS (ESI+) [C36H30N12]: calcd [M + 2H]2+ 316.13, found 316.26.3B porphyrins (200 µmol) were saponified in a refluxing solution of KOH  and EtOH (for methyl ester) or MeOH (for ethyl ester) (50 mL) for 24 h. After removal of the solvent, an excess of HCl was added until the green coloration of the solution appeared. The crude product was extracted in CHCl3/TEA , washed with distilled water, and dried over MgSO4. The residue was purified by silica gel column chromatography ) to obtain A3B porphyrins with deprotected carboxylic acid functions, as purple solids.Esters of A21H,23H-porphyrin):1b (5-(4-carboxyphenyl)-10,15,20-tri(4-pyridyl)- 178 µmol, yield 89%. 1H NMR : δ (ppm) = 9.40 , 8.97 , 8.93 , 8.87 , 8.58 , 8.42 ; MS (ESI+) [C42H27N7O2]: calcd [M + 2H]2+ 331.61, found 331.64.21H,23H-porphyrin):3b (5-(4-carboxyphenyl)-10,15,20-tri(4-imidazol-phenyl)- 182 µmol, yield 91%. 1H NMR : δ (ppm) = 8.83 , 8.35 , 8.23 , 7.77 , 7.62 , 7.24 ; MS (ESI+) [C54H36N10O2]: calcd [M + 2H]2+ 429.15, found 429.03.21H,23H-porphyrin):3c (5-(4-phenyoxyacetic)-10,15,20-tri(4-imidazol-phenyl)- 184 µmol, yield 92%. 1H NMR : δ (ppm) = 8.88 , 8.31 , 8.19 , 8.14 , 7.78 , 7.59 , 7.38 , 7.31 , 4.77 , −2.75 ; MS (ESI+) [C55H38N10O3]: calcd [M +2H ]2+ 444.15, found 444.17.N-methylimidazol-2-yl)-21H,23H-porphyrin):5b (5-(4-carboxyphenyl)-10,15,20-tri: δ (ppm) = 8.88 , 8.42 , 8.19 , 7.65 , 7.51 , 3.45 ; MS (ESI+) [C39H30N10O2]: calcd [M +2H]2+ 336.13, found 336.15.N-methylimidazol-2-yl)-21H,23H-porphyrin):5e (di(4-carboxyphenyl)- di: δ (ppm) = 8.85 , 8.43 , 8.19 , 7.67 , 7.47 , 3.44 , −2.78 ; MS (ESI+) [C42H30N8O4]: calcd [M + 2H]2+ 356.12, found 356.16.4 porphyrins, 45 eq for A3B porphyrins, 30 eq for A2B2 porphyrins) was added to a solution of porphyrin (1 eq) dissolved in anhydrous DMF (25 mL). The mixture was stirred for 3 h at 140 °C. DMF and excess iodomethane were removed with a rotary vane pump under heating (70 °C) to obtain N-methyl porphyrins in quantitative yields as light purple powders without further purification.An excess of iodomethane (60 eq for AN-methylpyridyl)porphyrin):2a : δ (ppm) = 9.49 , 9.17, 8.99 , 4.74 , −3.09 ; MS (ESI+) [C44H38I4N8]: calcd [M + H]4+ 169.83, found 169.81.N-methylpyridyl)-21H,23H-porphyrin):2b (5-(4-carboxyphenyl)-10,15,20-tri: δ (ppm) = 9.49 , 9.15 , 9.07 , 9.01 , 8.41 , 4.73 , −2.99 ; MS (ESI+) [C45H36I3N7O2]: calcd [M]2+ 353.14, found 352.65.N-methylimidazol-phenyl)porphyrin):4a : δ (ppm) = 10.13 , 8.93 , 8.65 , 8.53 , 8.27 , 8.14 , 4.10 , −2.88 ; MS (ESI+) [C60H50I4N12]: calcd [M]4+ 234.60, found 234.70.N-methylimidazol-phenyl)-21H,23H-porphyrin):4b (5-(4-carboxyphenyl)-10,15,20-tri: δ (ppm) = 10.13 , 8.93 , 8.89 , 8.65 , 8.54 , 8.42 , 8.36 , 8.26 , 8.14 , 4.10 , −2.88 ; MS (ESI+) [C57H45I3N10O2]: calcd [M]3+ 300.47, found 300.41.N-methylimidazol-phenyl)-21H,23H-porphyrin):4c (5-(4-phenyoxyacetic)-10,15,20-tri: δ (ppm) = 10.13 , 8.96 , 8.92 , 8.88 , 8.65 , 8.54  8.26 , 8.15 , 7.40 , 4.99 , 4.10 , −2.87 ; MS (ESI+) [C58H47I3N10O3]: calcd [M + H]3+ 310.79, found 310.75.N,N’-dimethylimidazol-2-yl)porphyrin):6a : δ (ppm) = 9.40 , 8.55 , 3.75 , −3.23 ; MS (ESI+) [C40H42I4N12]: calcd [M]4+ 172.59, found 172.54.N,N’-dimethylimidazol-2-yl)-21H,23H-porphyrin):6b (5-(4-carboxyphenyl)-10,15,20-tri: δ (ppm) = 9.23 , 8.52 , 8.47 , 8.39 , 3.75 , −3.03 ; MS (ESI+) [C42H39I3N10O2]: calcd [M]3+ 238.44, found 238.50.N,N’-dimethylimidazol-2-yl)-21H,23H-porphyrin):6e (di(4-carboxyphenyl) -di: δ (ppm) = 9.24–8.95 , 8.51 , 8.43 , 8.38 , 3.75 , −2.81 ; MS (ESI+) [C44H36I2N8O4]: calcd [M]2+ 370.14, found 370.04.10,15,20-tri(4-pyridyl)-21H,23H-porphyrin  was dissolved into a solution of HCl  under reflux for 3 h. After removal of the solvent in vacuo, the product was extracted in CHCl3/TEA , washed with distilled water, and dried over MgSO4. The solvent was removed to afford 1d as a purple powder with a quantitative yield.5-(4-acetamidophenyl)-1d:1H NMR : δ (ppm) = 9.02 , 9.02 , 8.81 , 8.16 , 7.98 , 7.08 ; MS (ESI+) [C41H28N8]: calcd [M + 2H]2+ 317.12, found 316.93.10,15,20-tri(4-pyridyl)-21H,23H-porphyrin was directly N-methylated, following the previous described procedure. Then, the crude was diluted in a solution of H2O/TFA  and stirred under reflux for 5 h. The aqueous solution was removed and the product was freeze-dried to obtain 2d as a purple-brown powder with a quantitative yield.5-(4-acetamidophenyl)-2d:1H NMR : δ (ppm) = 9.49 , 9.11 , 9.01 , 9.00 , 8.97 , 7.94 , 7.15 , 4.73 , −2.96 ; MS (ESI+) [C44H37I3N8]: calcd [M]3+ 225.77, found 225.74.F) were determined using a tetraphenyl porphyrin (TPP) solution in toluene as the fluorescence standard (ΦF = 0.11). The quantum yield of 1O2 production was determined by direct analysis of the 1O2 near-infrared luminescence at 1270 nm. Whereas TPP–COOH was used as standard in ethanol (ΦΔ = 0.54), tetra(N-methylpyridyl)porphyrin (2a) was chosen as the reference solution in D2O due to its high 1O2 quantum yield (ΦΔ = 0.90). Time-resolved experiments were performed using for excitation a pulsed laser diode emitting at 407 nm  coupled with a PDL 800-D driver , and for detection from an avalanche photodiode SPCM-AQR-15  coupled with a 550 nm long-wave pass filter as the detection system. Acquisition was performed by a PicoHarp 300 module with a PHR-800 4-channel router . Fluorescence decays were recorded using the single photon counting method. Data were collected up to 1000 counts accumulated in the maximum channel and analyzed using time-correlated single-photon counting (TCSPC) software  based on iterative reconvolution using a Levensberg–Marquandt algorithm, enabling the obtention of multi-exponential profiles . Singlet oxygen lifetime measurements were performed on a TEMPRO-01 spectrophotometer  composed of a SpectraLED-415 pulsed diode excitation source emitting at 415 nm, a cell compartment, a Seya-Namioka-type emission monochromator (600–2000 nm), and a H10330-45 near-infrared photomultiplier tube with a thermoelectric cooler  as the detection system. The system was monitored by a FluoroHub-B single-photon counting controller and the DataStation and DAS6 softwares (Horiba Jobin Yvon). Emission spectra were recorded on a Fluorolog FL3-22 spectrofluorometer  equipped with a 450 W Xenon lamp, a xenon flash lamp, a thermostated cell compartment (25 °C), and a R928 UV-visible photomultiplier . The system was monitored by a FluoroHub-B single-photon counting controller. The FluorEssence™ software (Horiba Jobin Yvon) was used for recording emission spectra. The DataStation and DAS6 softwares (Horiba Jobin Yvon) were used for phosphorescence lifetime measurements.Absorption spectra were recorded on a UV-3600 UV-visible double-beam spectrophotometer . Fluorescence spectra were recorded on a Fluorolog FL3-222 spectrofluorometer  equipped with a 450 W Xenon lamp, a thermostated cell compartment (25 °C), a UV-visible R928 photomultiplier , and an InGaAs infrared detector . The excitation beam was diffracted by a double-ruled-grating SPEX monochromator (1200 grooves/mm blazed at 330 nm). The emission beam was diffracted by a double-ruled-grating SPEX monochromator (1200 grooves/mm blazed at 500 nm). Singlet oxygen emission was detected through a double-ruled-grating SPEX monochromator (600 grooves/mm blazed at 1 μm) and a long-wave pass (780 nm). All spectra were recorded from solutions introduced in four-face quartz cuvettes. All the emission spectra (fluorescence and singlet oxygen luminescence) have been displayed with the same absorbance (less than 0.2) with lamp and photomultiplier correction. Fluorescence quantum yields (ΦS. aureus CIP76.25) and Gram-negative (P. aeruginosa CIP76110 and E. coli CIP54.8T) bacterial strains were obtained from Institut Pasteur . These strains were cultured in liquid tryptic soy  and incubated overnight at 37 °C under aerobic conditions. Square plates were kept warm inside a SR1000 Thermosi incubator. Bacterial concentrations were estimated by reading the turbidity at 600 nm in a JENWAY 6320D spectrophotometer . Antimicrobial experiments used a Heidolph Unkubator 1000 equipped with an Unimax 1010 orbital platform shaker . An Isotech Lightmeter 1335 light meter was used to measure the effective irradiation power .Gram-positive . Fresh solutions of porphyrin 2a, 4a, and 6a in DMSO were mixed with tryptic soy culture medium. The DMSO concentration never exceeded 1% (v/v). From these mixtures, 1 mL aliquots of serial dilutions (100 μM down to 156 nM) were transferred into two 24-well plates . Then, 1 mL of cultures containing 2 × 105 CFU/mL were deposited in each well. The 24-well plates were irradiated with LED visible light. The fluence rate (4.83 mW/cm²) was measured with a light meter. Plates were incubated under shaking (200 rpm) at 37 °C for 20 h . Controls consisting of 24-well plates were prepared in the same conditions but kept in the dark. Six independent experiments were performed with each strain. The bacterial count was performed after a 10-fold serial dilution of each well. Each dilution was spread on tryptic soy agar plates using an automatic plater . After incubation at 37 °C for 24 h, colonies were counted to determine the total CFU per mL (CFU/mL). The minimum bactericidal concentration (MBC) corresponds to the concentration of the active compound for which 99.9% of the bacteria have been killed .A9 CFU/mL) were incubated for 30 min at 37 °C in the dark with 1 mL of the different solutions . Then, bacteria were collected by centrifugation  and washed twice with PBS 1 × (without Ca2+ and Mg2+). Washed bacteria were resuspended in PBS, transferred into a 96-well plate, and irradiated by white LEDs (4.83 mW/cm²). Survival rates, calculated in relation to the initial count of each bacterial culture, were plotted as a function of cumulative fluence (J/cm²). Four independent experiments were performed with each strain.To observe the effects of light fluence (J/cm²) on the survival rate of each strain, bacteria  or emissions quenching (due to the presence of primary amine functions). Even if the participation of a carboxylic acid function leads to emission quenching of these PS (as a consequence of an ICT), phenylimidazolium porphyrins have shown several advantages, as easier synthesis, consistent photophysical properties (similar to those of TPP), along with a significantly high photoinactivation activity against S. aureus and E. coli. Finally, the methylimidazolium groups have not a strong electron-withdrawing effect on the porphyrin core, which allows the designing of cationic PSs with different chemical functions without any emissions quenching due to potential ICT/IET. Whereas 6a showed less efficiency against bacteria, likely due to lower oxygen singlet production, porphyrin 6e has a significant singlet oxygen production. Thus, further photobactericidal studies on porphyrins 6 should focus on compounds bearing two targeting groups.In order to photoinactivate MDR strains, previous studies have highlighted the efficiency of cationic PS, including pyridinium porphyrins. In this work, different families of cationic porphyrin have been investigated to support future studies. Even if pyridinium A


Polymeric nanoparticles can be used for drug delivery systems in healthcare. For this purpose poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) offer an excellent polymeric matrix. In this work, PLGA and PEG polymers were functionalized with coumarin and carbohydrate moieties such as thymidine, glucose, galactose, and mannose that have high biological specificities. Using a single oil in water emulsion methodology, functionalized PLGA nanoparticles were prepared having a smooth surface and sizes ranging between 114–289 nm, a low polydispersity index and a zeta potential from −28.2 to −56.0 mV. However, for the corresponding PEG derivatives the polymers obtained were produced in the form of films due to the small size of the hydrophobic core. Described as the manipulation of atomic matter, nanotechnology was described theoretically in the 1960s by Richard Feynman, and the practice emerged a decade later. After Taniguchi’s, Drexler’s, and other scientist’s valuable contributions, nanomedicine has developed  and receSuitable nanoparticles are capable of transporting drugs in a targeted manner to a specific tissue, cell or organ, minimizing the toxic effects and high therapeutic doses inherent in most current pharmacological treatments ,4,5. RecDepending on the application , different types of nanoparticles have been proposed, and these can be divided into two main groups: organic and inorganic nanoparticles. In the first group are dendrimers, liposomes, and polymeric nanoparticles. The second group includes quantum dots, silica, gold, and silver nanoparticles. Due to the high rate of tissue accumulation, that can result in toxicity problems, nanoparticles that cannot be degraded by the body are not as popular and attractive as biodegradable and biocompatible polymeric nanoparticles (PNPs) ,8.PNPs play an important role in therapeutic applications, such as encapsulation and controlled drug release ,10. The Targeted drug delivery, also known as “magic bullet”, is a scientific concept proposed by Paul Ehrlich in 1900, and is the ability to selectively eliminate pathogenic microorganisms without harming the patient themselves, intending that the drug only acts on its intended target. Unlike most currently available treatments, PNPs capable of targeting drug delivery to a particular tissue, cell or organ can be achieved if the surface of the PNP is functionalized accordingly  ,21. HighWith all of this in mind, we have attempted to functionalize commercial polymers, namely poly(ethylene glycol) (PEG) and poly(lactic-co-glycolic acid) (PLGA), in order to obtain drug delivery agents, either pro-drugs or nanoparticles for drug encapsulation. Monosaccharides  were bonded to these polymers to allow specific interactions between cell receptors and drug delivery agents. Coumarins were also included to potentially increase the pharmaceutical activity of these polymers, since they are known for their biological properties ,24,25,26Our synthetic strategy began with the preparation of ligands that would be bonded to poly(ethylene glycol) (PEG) and poly(lactic-co-glycolic acid) (PLGA) polymers. We wanted these bonds to be strong, but also easily formed, and both 1,2,3-triazole ring and amide linkages present those features, whereby coumarins, carbohydrates and the polymers were modified accordingly, as described below.1 in 60% yield  were in accordance with those already reported in the literature. For propargylated coumarin 4, methylene protons were observed at 4.77 ppm, and the alkyne proton at 2.58 ppm. Alkyne stretch bands were observed at 3266 and 2119 cm−1. Coumarin 5 presented the methylene proton signal at 4.95 ppm and the alkyne proton at 2.56 ppm. FT-IR spectrum presented the alkyne stretches at 3315 and 2117 cm−1. Ester hydrolysis of 2 was accomplished with sodium hydroxide in ethanol at 80 °C, affording 3 in 95% yield.Propargylation reactions of 7 was prepared. Due to its high volatility and reactivity, 7 was always maintained in diethyl ether, even for its quantification and characterization. Subsequent triazole ring formation with coumarin 6, afforded 8 in good yield , and the products were mixtures of α and β anomers, with a 2:1 ratio. This ratio was calculated taking advantage of the vicinal coupling constants characteristics for hexoses , and with 1JH-C coupling constant for mannopyranose 11. Benzylation of α and β propargyl glucopyranosyl mixtures afforded the per-O-benzylated anomers, which could be separated by column chromatography, using 6:1 hexane/ethyl acetate as eluent.Insertion of a triazole ring between the carbohydrate moiety and the coumarin/polymer moieties not only increases the linkage strength, but mimics the amide group, which can induce, or improve, the biological activity of the final compounds. Propargylation of glucose, galactose, and mannose  using im9, afforded 12. Subsequent triazole formation with azide 7 afforded 13 in good yield. De-acetylation using sodium methoxide led to the corresponding product 14 , and catalytic 4-dimethylaminepyridine , which is within the expected values. This is a very important result, since the other PEG hydroxyl should be free to link to the carbohydrate moiety. A 13C NMR spectrum supports the esterification success through coumarin signals between 117 and 163 ppm. The terminal hydroxyl of ester 17 was then tosylated to provide ester 18, in good yield. A tolyl methyl proton signal was observed at 2.45 ppm and a corresponding carbon signal at 21.6 ppm. Aromatic proton signals where observed between 7.90 and 7.32 ppm, and between 136.5 and 115.5 ppm in the carbon spectrum. The tosyl group was substituted using sodium azide in DMF, affording the azide 19 in very good yield. Product formation was confirmed by the absence of tosyl signals both in the proton and carbon spectra, and by the observation of an azide stretch band in the FT-IR at 2104 cm−1. Cycloaddition with the previously prepared propargyl galactopyranose 10 using catalytic CuI, and diisopropylethylamine (DIPEA) in freshly distilled tetrahydrofuran (THF) afforded the desired triazole-containing glycoconjugate 20 in only 18% yield. The poor yield obtained is believed to be due to copper complexation with the free hydroxyls of propargyl galactopyranose. Adding 2,2’-bipyridyl in excess to the reaction mixture, did not improve this result  affording 45% of propargylated galactopyranose opadhyay . [α]D16=11 as a yellowish oil . Sulfuric acid supported on silica was prepared accordingly to the procedure described by Roy and Mukhopadhyay [max: 3289 (br), 2930 (w) cm−1; 1H NMR  δ: 5.00 , 4.40–4.20 , 3.92 , 3.89–3.81 , 3.81–3.69 , 3.69–3.57 , 2.89 ; 13C NMR  δ: 98.7 (C-1α), 79.0, 76.3, 73.1, 70.5, 69.9, 66.6, 60.8, 54.6 (C-1’).D-mannose , propargyl alcohol  and sulfuric acid supported on sílica (58 mg) were mixed together under magnetic stirring and argon atmosphere. The reaction flask was heated at 65 °C overnight, and after cooling the mixture was purified by column chromatography  affording propargylated mannopyranose opadhyay . FT-IR  reacted with acetic anhydride  in dry pyridine (30.0 mL) for 4 h under an argon atmosphere. The solvent was then evaporated and the remaining solid was dissolved in dichloromethane and purified by silica column chromatography using hexane/ethyl acetate (1:1) affording 12 as a colorless oil . FT-IR (NaCl) ῡmax: 3278 , 2961 , 1749  cm−1; 1H NMR  δ: 5.49 , 5.30–5.27 , 5.15–4.97 , 4.92 , 4.78 , 4.38 , 4.28 , 4.26 , 4.18–4.03 , 3.78–3.70 , 2.48 , 2.46 , 2.06 .Glucopyranoside 7  was dissolved in 4,0 mL of freshly distilled THF, and DIPEA , copper iodide  and 12  were added. After 2.5 h the solvent was evaporated and the mixture was purified by column chromatography using chloroform/methanol (9:1), affording 13  as a yellow solid. m.p. = 60–65 °C (degradation); FT-IR (NaCl) ῡmax: 3421 , 1745  cm−1; 1H NMR  δ: 7.68 , 7.64 , 5.49 , 5.22 , 5.09 , 4.91–4.83 , 4.70 , 4.44 , 4.31–4.22 , 4.11 , 3.75 , 3.26 , 2.13–1.98 ; 13C NMR  δ: 170.7–169.5 (C-Ac), 144.1 (C-4’β), 143.5 (C-4’α), 123.7 (C-5’β), 123.6 (C-5’α), 99.9 (C-1α), 95.0 (C-1β), 72.8–72.0 (C-5), 71.9–71.3 (C-2), 70.7–70.6 (C-3), 68.5–68.3 (C-6), 67.5 (C-4), 63.0 (C-6’), 61.8 (C-6β), 61.3 (C-6α), 60.8 (C-7’), 41.7 (C-8’), 20.8–20.6 (CH3).Compound 13  was dissolved in dry methanol at ice-bath temperature, and sodium methoxide was added . The reaction was allowed to warm to room temperature and stirred for a further 3 h. Pre-activated and thoroughly washed acidic Dowex was added until the pH changed from basic to acidic. The solution was filtered and the solvent evaporated to give compound 14  as a white foam. Due to the complex anomeric mixture this compound’s characterization was based on the spectra of per-O-acetyl compound 13.Compound 15 were filtered and washed with cold ethanol . m.p. = 189–191 °C; FT-IR (NaCl) ῡmax: 3374 , 3067 , 2924 , 1724–1694  cm−1; 1H NMR  δ: 11.31 , 7.79 , 7.47 , 7.38 , 6.15 , 5.43 , 4.26 , 4.19–4.15 , 3.86 , 2.41 , 2.19–2.04 , 1.77 ; 13C NMR  δ: 163.6 (C-9), 150.4 (C-10), 145.1 (C-11), 135.9 (C-14), 132.1 (C-6), 130.2 (C-13), 127.6 (C-12), 109.8 (C-7), 84.0 (C-1), 83.2 (C-4), 70.1 (C-3), 69.9 (C-5), 38.3 (C-2), 21.1 (C-15), 12.1 (C-8).In a round bottom flask 2’-deoxythymidine  was dissolved in dry pyridine (7.5 mL) and the flask cooled in an ice bath for 1 h. Tosyl chloride  dissolved in dry pyridine (2.5 mL) was added dropwise and the reaction allowed to attain room temperature during 17 h. The solvent was then evaporated, and the resulting crude product was dissolved in ethanol at 75 °C and then cooled down to −10 °C for 12 h. The resulting crystals of 15  was dissolved in DMF (5.0 mL), and sodium azide was added . The reaction mixture was heated to 85 °C on an oil bath for 15 h. The solvent was then evaporated under reduced pressure and the mixture was purified by silica gel column chromatography using chloroform/methanol (9:1) as eluent, affording 16  as a beige solid.Method I—conventional heating: compound 15  was dissolved in DMF (5.0 mL), and sodium azide  was added. The mixture was irradiated with microwaves with a power of 250 W at a temperature of 100 °C, for two 1 min cycles. The solvent was evaporated under reduced pressure and the mixture was purified by column chromatography  to afford 16  as a beige solid. m.p. = 156–158 °C; FT-IR (NaCl) ῡmax: 3422 , 2926 , 2103 , 1701–1685  cm−1; 1H NMR  δ: 7.56 , 6.29 , 4.38 , 3.99 , 3.63 , 2.37–2.25 , 1.92 ; 13C NMR  δ: 166.3 (C-9), 152.3 (C-10), 137.8 (C-6), 111.9 (C-7), 86.4 (C-4), 86.3 (C-1), 72.5 (C-3), 53.4 (C-5), 40.2 (C-2), 12.5 (C-8).Method II—microwave irradiation: compound 1000  was added. The reaction flask was heated at 40 °C for 18 h. Then, the mixture was filtrated and washed two times with aqueous acetic acid 5% (2 × 20 mL) and once with water (20 mL). The organic phase was dried over sodium sulfate, filtered, concentrated and purified by column chromatography (chloroform to 9:1 chloroform/methanol gradient), affording the required product in 98% yield  as a yellowish wax. FT-IR (NaCl), ῡmax: 3512 , 2870 , 1766  cm−1; UV (DCM) λmax = 292 nm; Em (DCM) λmax = 386 nm (λexc = 320 nm); 1H NMR  δ: 8.57 , 7.65 , 7.36 , 4.50 , 3.85 , 3.79–3.56 ; 13C NMR  δ: 162.8 (C-9), 156.6 (C-2), 155.2 (C-8ª), 148.8, 134.4 (C-Ar), 129.6 (C-Ar), 124.9 (C-Ar), 119.9, 119.8 (C-3 and C-4a), 116.8 (C-Ar), 72.5 (PEG), 70.5 (PEG), 70.2 (PEG), 68.9 (O-CH2-CH2-PEG), 64.8 (O-CH2-CH2-PEG), 61.6 (PEG).Coumarin 3-carboxylic acid  was dissolved in DCM (15 mL) with magnetic stirring and under an argon atmosphere. DCC  and DMAP  were added. After 45 min, a white precipitate was observed and PEG17  was dissolved in DCM (25 mL) and triethylamine  with magnetic stirring and argon atmosphere. Tosyl chloride  was then added slowly in portions. After 18 h, the reaction mixture was evaporated and purified by column chromatography , to afford 18 as a yellowish wax in 92% yield . FT-IR (NaCl), ῡmax: 2872 , 1761 , 1108  cm−1; UV (DCM) λmax = 285 nm; Em (DCM) λmax = 412.5 nm (λexc = 320 nm); 1H NMR  δ: 8.57 , 7.80 , 7.73–7.57 , 7.35 , 4.50 , 4.16 , 3.89–3.81 , 3.76–3.49 , 2.45 ; 13C NMR  δ: 162.8 (C-9), 156.6, 155.2, 148.9 (C-4), 144.8, 134.5, 133.0, 129.8, 129.6, 128.0, 124.9, 117.9, 117.8, 116.8, 70.7, 70.6, 70.6, 70.5 (PEG), 69.3 (PEG), 68.9 (PEG), 68.6 (PEG), 64.9 (PEG), 21.6 (C-14).Polymer 18  was dissolved in DMF (32 mL) and sodium azide  was added in portions with stirring under an argon atmosphere. After 18 h, the DMF was evaporated under reduced pressure and water was added to the resulting residue. The mixture was extracted with DCM, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography , to afford the product as an orange wax , and used for further reactions. FT-IR (NaCl), ῡmax: 2871 , 2104  1761  cm−1; UV (DCM) λmax = 284 nm; Em (DCM) λmax = 412.5 nm (λexc = 320 nm); 1H NMR  δ: 8.57 , 7.79–7.56 , 7.46–7.31 , 4.58–4.41 , 4.02–3.33 ; 13C NMR  δ: 162.8 (C-9), 156.6 (C-2), 155.2 (C-8a), 148.9, 134.5, 129.6, 124.9, 117.9, 117.9, 116.8, 70.6 (PEG), 50.7 (CH2N3).Polymer 19  was dissolved in THF (4.2 mL) then copper iodide , DIPEA  and compound 10  were added. The mixture was magnetically stirred under an argon atmosphere for 34 h. After removal of the solvent under reduced pressure, the residue was suspended in DCM and washed twice with water, once with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification by preparative chromatography (95:5 chloroform/methanol) afforded 20 as a yellow wax in 18% yield . FT-IR (NaCl), ῡmax: 3458 (O-H st), 2876 (C-H st), 1759 (C=O st) cm−1. UV (DCM) λmax = 293 nm; Em (DCM) λmax = 413 nm (λexc = 320 nm); 1H NMR  δ: 8.57 , 8.23–7.99 , 7.72–7.61 , 7.40–7.32 , 5.05 , 4.87 , 4.74 , 4.62 , 4.50 , 4.30–3.34 ; 13C NMR  δ: 162.8, 156.6, 155.2, 149.2 (C-4), 148.9, 134.5 (C-7), 129.6 (C-5), 124.9 (C-9’ and C-6), 117.9, 117.9, 116.8 (C-8), 98.8 (C-1’), 70.5 (PEG), 69.9 (C-2’), 69.0 (C-4’), 68.9 (PEG), 64.9 (C-7’), 62.1, 60.3 (C-6’), 52.9, 51.1 (C-3’).Azide polymer 21  as a yellowish wax. FT-IR (NaCl), ῡmax: 3511 , 2873  cm−1; 1H NMR  δ: 7.80 , 7.35 , 4.16 , 3.75–3.49 , 3.38 , 2.45 ; 13C NMR  δ: 144.8 (C-Ar), 133.1 (C-Ar), 129.8 (C-Ar), 128.0 (C-Ar), 70.8 (PEG), 70.6 (PEG), 70.6 (PEG), 69.3 (PEG), 68.7 (PEG), 21.6 (CH3).PEG  was dissolved in DCM (50 mL) with magnetic stirring and an argon atmosphere. Triethylamine  and tosyl chloride  were added and the reaction mixture was heated at 50 °C for 15 h. The mixture was concentrated under vacuum and purified by column chromatography (chloroform to 9:1 chloroform/methanol gradient) affording quantitatively the product 21  in DMF (18 mL) under magnetic stirring and argon atmosphere was added sodium azide  and the reaction was heated at 50 °C for 16 h. The solvent was evaporated under reduced pressure and then dichloromethane (35 mL) was added and the organic phase was washed twice with brine (2 × 20 mL) and once with water (20 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (chloroform to 9:1 chloroform/methanol stepwise) affording product 22  as a yellowish wax; 1H NMR  δ: 3.65 , 3.39 ; 13C NMR  δ: 70.7 (PEG), 70.7 (PEG), 70.6 (PEG), 70.6 (PEG), 70.0 (PEG), 50.7 (2× CH2N3).To a solution of compound 22  and 4 , copper iodide , and DIPEA  were mixed in THF (8 mL) under magnetic stirring and an argon atmosphere for 18 h. The solvent was evaporated under reduced pressure and then dichloromethane (35 mL) was added. The resulting organic phase was washed three times with water (3 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography  affording product 23  as an orange wax. FT-IR (NaCl) ῡmax: 3553  2872 , 2106 , 1732 , 1614  cm−1; UV (DCM) λmax = 322 nm; Em (DCM) λmax = 386 nm (λexc = 320 nm); 1H NMR  δ: 8.00 , 7.66 , 7.41 , 7.03–6.88 , 6.26 , 5.29 , 4.60 , 3.90 , 3.82–3.54 , 3.39 ; 13C NMR  δ: 161.4 (C-2’), 161.0 (C-7’), 155.7 (C-8a’), 143.4 (C-4), 142.4 (C-6’), 129.0 (C-4’), 124.8 (C-8’), 113.4 (C-5’), 113.0 (C-4a’), 112.8 (C-5), 102.1 (C-3’), 70.7 (PEG), 70.6 (PEG), 70.5 (PEG), 70.4 (PEG), 70.3 (PEG), 70.0 (PEG), 69.3 (PEG), 62.1 (C-6), 50.7 (2× CH2-N3).Compounds 4 , propargylated galactopyranosyl 10 , copper iodide , DIPEA , and 2,2’-bipyridine  were dissolved in THF (1 mL), and mixed together under magnetic stirring and argon atmosphere for 22 h. The mixture was evaporated under reduced pressure, and the residue was dissolved in chloroform (10 mL), washed two times with deionized water (10 mL), once with brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography  to afford 24  as an orange wax. λ Absmax = 321 nm; λ Emmax = 383.5 nm (λexc = 320 nm); 1H NMR  δ: 7.93 , 7.66 , 7.40 , 7.02–6.91 , 6.27 , 5.32–5.24 , 5.10–5.00 , 4.93–4.66 , 4.65–4.47 , 4.47–4.20 , 4.19–3.99 , 3.95–3.78 , 3.78–3.39 , 3.24–3.05 ; 13C NMR  δ: 161.4 (C-2), 161.1 (C-7), 155.7 (C-8a), 143.4 (C-4), 142.6 (C-10 and C-13), 128.9 (C-5), 124.6 (C-11 and C-12), 113.3 (C-13), 112.9 (C-4a), 112.8 (C-6), 102.1 (C-8), 72.7 (PEG), 70.5 (PEG), 69.3 (PEG), 62.3 (C-9), 61.6 (PEG), 50.4 (C-14).Azide 4 , propargylated mannopyranosyl 11 , copper iodide , DIPEA  and 2,2’-bipyridine  were dissolved in THF (1 mL), and mixed together under magnetic stirring and argon atmosphere for 22 h. The mixture was evaporated under reduced pressure, and the residue was dissolved in chloroform (10 mL), washed two times with deionized water (10 mL), once with brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography  to afford 25  as an orange wax. λ Absmax = 321 nm; λ Emmax = 386.5 nm (λexc = 320 nm); 1H NMR  δ: 8.01–7.81 , 7.66 , 7.41 , 7.05–6.88 , 6.27 , 5.35–5.22 , 5.11–4.90 , 4.85–4.64 , 4.63–4.48 , 4.31–2.97 ; 13C NMR  δ: 161.4 (C-2), 161.1 (C-7), 155.7 (C-8a), 143.4 (C-4), 142.7 (C-10 and C-13), 129.0 (C-5), 124.6 (C-11 and C-12), 113.4 (C-3), 112.9 (C-4a), 112.9 (C-6), 102.1 (C-8), 72.7 (PEG), 70.5 (PEG), 69.4 (PEG), 69.0 (PEG), 62.3 (C-9), 50.4 (C-14).Azide 3 , DMAP  and coupling agent DCC  were stirred in DCM (7 mL) for 30 min. Then, PEG  was added. After 16 h, DCM (10 mL) and acetic acid solution  were added to the reaction mixture. After 1 h the organic phase was separated and washed with deionized water (2 × 10 mL), dried over anhydrous sodium sulfate, filtered, evaporated and purified by silica gel column chromatography using chloroform/methanol 9:1, affording 26  as a yellow wax. FT-IR (NaCl) ῡmax: 3259 , 3008 , 2929 , 1733 (s), 1701  cm−1; 1H NMR  δ: 7.47 , 6.98 , 4.82 , 4.23 , 3.66 , 2.98 , 2.66 , 2.57 , 2.45 , 2.34 ; 13C NMR  δ: 172.9 (C-15), 161.7 (C-2), 157.4(C-7), 151.4 (C-9), 147.5 (C-4), 122.5 (C-5), 121.7 (C-3), 115.0 (C-10), 114.7(C-8), 108.3 (C-6), 78.2 (C-2’), 77.3 (C-3’), 70.6 (CH2-PEG), 63.7 (C-16), 56.4 (C-1’), 32.6 (C-14), 23.1 (C-13), 15.0 (C-12), 8.3 (C-11).Compound 26 , DIPEA , copper iodide  and compound 16  were stirred in THF (4.0 mL) for 3 h. After solvent evaporation the mixture was dissolved in dichloromethane and purified by column chromatography using hexane/ethyl acetate (1:1) as eluent, affording 27  as a yellow wax. 1H-NMR  δ: 7.77 , 7.41 , 7.30 , 6.98 , 6.24 , 4.70 , 4.47 , 4.20 , 4.02 , 3.60 , 2.95 , 2.62 , 2.40–2.25 , 1.92–1.86 ; 13C-NMR  δ: 172.9 (C-15), 163.8 (C-9’’), 161.9 (C-2), 158.1 (C-7), 151,3 (C-9), 150.4 (C-10’’), 147.9 (C-4), 143.8 (C-4’), 135.5 (C-5’), 124.8 (C-6’’), 122.8 (C-6), 121.3 (C-3), 114.7 (C-10), 114.1 (C-8), 111.4 (C-7’’), 108.3 (C-5), 84.9 (C-1’’), 84.5 (C-4’’), 71.5 (C-3’’), 71.2 (C-3’’), 70.5 (C-PEG), 63.7 (C-16), 52.3 (C-5’’), 51.3 (C-6’), 40.2 (C-2’’), 32.6 (C-14), 23.1 (C-13), 15.0 (C-12), 12.6 (C-8’’), 12.4 (C-8’’), 8.3 (C-11).Compound 14  was dissolved in 4 mL of DMF, and commercially available polymer poly  was added. To the stirred reaction mixture, methanesulfonic acid  was added and the reaction proceeded overnight at 65 °C. The solution was cooled down, and 4 mL of cold water was added. The precipitated polymer was collected by filtration to give the PLGA derivative 28  as a white solid.Compound 8  was dissolved in 4 mL of DMF, and poly  was added and this mixture stirred at room temperature. Methanesulfonic acid  was added, and heated overnight at 65 °C. The solution was cooled and 4 mL of cold water was added. The precipitated polymer was collected by filtration to give the PLGA derivative 29  as a white solid.Compound The use of these two polymeric building blocks (PEG and PLGA) has allowed us to prepare a new type of macromolecule functionalized with carbohydrate and coumarin moieties. The polymer PEG was selectively functionalized making possible the production of asymmetric macromolecules that contain at one terminal the carbohydrate unit and at the other the coumarin molecule. This asymmetry provides the ability to obtain a self-assembling control during the nanoparticles oil in water transformation. This kind of macromolecules showed a tendency to form aggregates with sizes ranging between 220 and 580 nm, respectively, but the majority of the sample presented a polymeric film after the medium evaporation. This film formation can suggest that the hydrophobic core is not big enough to provide the desired self-assembling effect. PLGA has been successfully functionalized and transformed into stable and spherical nanoparticles with a smooth surface, with practically no aggregation. The size of these different particles ranges between 114–289 nm with a zeta potential value of −28.2 mV for the glucoconjugate and −56.0 mV for the coumarin-containing derivative. Using a single oil in water emulsion technique, it was possible to obtain low polydispersity indexes for all PLGA nanoparticles.


Sacrophyton. The total number of species belonging to it was estimated to be 40. Sarcophyton species are considered to be a reservoir of bioactive natural metabolites. Secondary metabolites isolated from members belonging to this genus show great chemical diversity. They are rich in terpenoids, in particular, cembranoids diterpenes, tetratepenoids, triterpenoids, and ceramide, in addition to steroids, sesquiterpenes, and fatty acids. They showed a broad range of potent biological activities, such as antitumor, neuroprotective, antimicrobial, antiviral, antidiabetic, antifouling, and anti-inflammatory activity. This review presents all isolated secondary metabolites from species of genera Sacrophyton, as well as their reported biological activities covering a period of about two decades (1998–2019). It deals with 481 metabolites, including 323 diterpenes, 39 biscembranoids, 11 sesquiterpenes, 53 polyoxygenated sterols, and 55 miscellaneous and their pharmacological activities. One of the most widely distributed soft coral species, found especially in shallow waters of the Indo-Pacific region, Red Sea, Mediterranean Sea, and also the Arctic, is genus  Sarcophyton covers 35 species, and another six species of Sarcophyton were described -3,8-decadienyl acetate 26, (3E)-7-hydroxy-4,8,15,15-tetramethyl-1-[(Z)-12-methyl-10-oxo-12-pentenyl]-3,8-decadienyl acetate 27 beside sarcoglaucol 28, and decaryiol 29, were isolated form S. cherbonnieri. Spectral data showed that compound 25 was a 16-keto derivative of compound 28 and the 13-hydroxy derivative of compound 24 -hexadeca-4,12,14-trien-18-one 30, and -sarcophytolide 31, in addition to sarcophytolide 32, -9-Hydroxy-1-isopropyl-8,12-dimethyloxabicyclo[9.3.2]-hexadeca-4,12,14-trien-18-one 33 and -1-Isopropyl-8,12-dimethyl-18-oxo-oxabicyclo[9.3.2]-hexadeca-4,12,14-trien-2-yl acetate 34, were reported from Sarcophyton new sp. Additionally, the authors presented biosynthetic pathways for all isolated compounds which resulted from the common acyclic precursor -geranylgeranyl pyrophosphate (GGPP), by converting geranylgeranyl-PP [GGPP] into geranylneryl-PP [GNPP], using diterpene synthase, followed by cyclization to cembranoid ring with a 12Z double bond propan-2-ol 209, -1-(2-methoxy-propan-2-yl)-4,8,12-trimethyloxabicyclo[12.1.0]-pentadeca-1,3,11-triene 210, crassumol C 211, and laevigatol A 212.  dodecane skeleton named, sarinfacetamides A and B 315 and 316 and a known compound; nanolobatin B 317 were reported. Their structures were clarified by a thorough spectral data, TDDFT-ECD calculation and the absolute configuration of sarinfacetamide A 315 was investigated. The authors proposed a probable biosynthetic pathway for sarinfacetamides A and B 315 and 316, in which, the development of the carbon-12−carbon-4 bond together with epoxide ring opening of nanolobatin B 317 created an intermediary carbon cation molecule which reacted with the nitrogen lone pair electrons attacking carbon-9 followed by the opening of carbon-1/carbon-9 bond and generation of carbon-1/carbon-8 bond offering sarinfacetamides skeleton, of which acetylation of carbon -4/carbon -8 or carbon -4/carbon -8/carbon -16 yielded sarinfacetamides B 316 and A 315, respectively  hexadecane skeleton, along with diterpenoids sarcophytol M 322, were isolated from S. mililatensis. Absolute configuration for sarcomililatol A 319 and sarcomililate A 321 were elucidated by combination of residual dipolar coupling-based NMR analysis, Snatzke’s assay and TDDFT-ECD calculation and anomalous X-ray diffraction with sarcomililatol A 319. The authors also proposed a biogenetic pathway relationship for sarcomililatols A, B and sarcomililate A 319–321. Based on structural resemblance between the three compounds, acetylation of sarcomililatol B 320 gave sarcomililatol A 319, and with dehydration under acid, isomerization and intramolecular [4 + 2] cycloaddition, sarcomililate A 321 was formed D +25.8° (−)-alloaromadendrene and cyclosinularane 365 [Investigation of the methylene chloride extract of rane 365 .366 and 367 were isolated from S. buitendijki and their structures were elucidated through 1 and 2D NMR [368, was isolated from S. glaucum [Two guaiane sesquiterpenes 4α-ethoxy-10α-hydroxyguai-6-ene and 10α-hydroxy-4α-methoxyguai-6-ene d 2D NMR . One 1,2 glaucum .369 was isolated from S. trocheliophorum ethyl acetate extract. Through spectral data, its structure was elucidated, revealing that it could be the result of aromatization with dehydration of ring B of sarcophytin which co-exist in the extract, and removal of ring C and the ring junction methyl and breakage of ring A [370 from S. trocheliophorum was reported [371 and 1,4-peroxymuurol-5-ene 372 from S. ehrenbergi were stated. [S. glaucum sesquiterpenoid, 6-oxo-germacra-4(15),8,11-triene 373 was also reported [Sacrophyton sp.Trocheliophorin f ring A . In addireported . Moreove stated. . Continureported . Figure E-en-3β,5α,6β,20(S)-tetraol 374, along with 24-methylcholestane-3β,5α,6β,25-tetraol-25-monoacetate 375 and gorosten-5(E)-3β-ol 376, were reported from S. trocheliophorum. Interpretation using 1 and 2D NMR analysis pointed out the existence of 23,24-dimethyl cholesterol derivatives which were further approved by the mass fragmentation pattern [S)-24methylcholestane-3β,5α,6β-triol 377 from S. crassocaule were also reported [One polyhydroxysetrol, 23,24-dimethylcholest-16(17)- pattern . The isoreported .378 was isolated from S. digitatun Moser. The carbon NMR matched that of (22R)-methylcholest-5-en-3β, 22,25,28-tetraol-3,22,28-triacetate 379 indicating that sardisterol 378 has the same steroidal nucleus as (22R) -methylcholest-5-en-3β, 22,25,28-tetraol-3,22,28-triacetate 378 but the OH groups in carbon 22 and 28 were replaced by acetoxy groups [Sardisterol y groups .S)-24-methylcholestane-3β,5α,6β,25γ,26-pentol-25,26-diacetate 380 and (24S)-24-methylcholestane-3β,5α,6β,25γ,26-pentol-26-n-decanoate 381, was isolated from S. trocheliophorum, while, (24S)-24-methylcholestane-3β,5α,6β,25γ-tetrol 382 and (24S)-24- methylcholestane-3β,5α,6β,25γ pentol-25-monoacetate 383 were reported from S. glaucum [-11α-acetoxy-ergostane-22,25-dien-3β,5α,6β-triol 385, (24S)-ergostane-1α,3β,5α,6β,11α-pentaol 386, (24S)-23,24-dimethylcholesta-22-en-3β,5α,6β,11α-tetraol 387, -23,24-dimethylcholesta-17(20)-en-3β,5α,6β-triol 388, 11α-acetoxy-gorgostane-3β,5α,6β,12α-tetraol 389 and 12α-acetoxy-gorgostane-3β,5α,6β,11α-tetraol 390, sarcoaldosterol A 391, (24S)-ergostane-3β,5α,6β-triol 392, (24S)-ergostane-3β,5α,6β,11α-tetraol 393, (24S)-ergostane-7-en-3β,5α,6β-triol 394, 11α-acetoxy-gorgostane-3β,5α,6β-triol 395, sarcoaldosterol B 396 and gorgostane-1α,3β,5α,6β,11α-pentaol 397. Structural elucidation for all isolates were done based on spectral analysis and comparing with reported literature [Fourteen polyoxygenated steroids with 3β,5α,6β-hydroxy group, showing ergostane, cholestane, gorgostane and 23,24-dimethyl cholestane carbon skeletons were reported from terature .S)-ergostan-3β,5α,6β,25-tetraol-25-monoacetate 398, (24S)-24-methylcholestan-3β,6β,25-triol-25-O-acetate 399, (24S)-methylcholestan-3β,5α,6β,25-tetraol-3,25-diacetate 400, (24S)-24-methylcholestan-1β,3β,5α,6β,25-pentaol-25-monoacetate 401 and (24S)-methylcholestan-3β,5α,6β,12β,25-pentaol-25-O-acetate 402, were reported from Sarcophyton sp., one was reported as 18-oxygenated polyhydroxy steroid, (24S)-ergostan-3β,5α,6β,18,25-pentaol 18,25-diacetate 403. The structure of this compound was determined through spectroscopic data, and its absolute configuration was elucidated by the modified Mosher’s assay [Six polyhydroxy steroids, -11α-acetoxy-16β-methoxy-23,24-dimethylcholest-17(20)-en-3β,5α,6β-triol 406, (24R)-gorgost-25-en-3β,5α,6β,11α-tetraol 407 and 11α-acetoxycholest-24-en-1α,3β,5α,6β-tetraol 408, (24R)-methylcholest-7-en-3β,5α,6β-triol 409, 11α-acetoxy-cholest-24-en-3β,5α,6β-triol 410, -11α-acetoxy-ergost-22,25-dien-3β,5α,6β-triol 411, (24S)-11α-acetoxy-ergost-3β,5α,6β-triol 412, (24R)-11α-acetoxy-gorgost-3β,5α,6β-triol 413, (24S)-ergost-3β,5α,6β,11α-tetraol 414, and (24S)-23,24-dimethylcholest-22-en-3β,5α,6β,11α-tetraol 415. Their structural elucidation was based on spectral data, and it was found that all isolated compounds have a distinguishable 3β,5α,6β-trihydroxy group; however, they differ in side chains and substitutions. These steroids could be alienated structurally into four categories including, cholesterol, ergosterol, gorgosterol and 23,24-dimethyl cholesterol. -11α-acetoxy-16β-methoxy-23,24-dimethylcholest-17(20)-en-3β,5α,6β-triol 406 has a distinctive 17(20)-en-23,24-dimethyl side chain, while (24R)-gorgost-25-en-3β,5α,6β,11α-tetraol 407 was a gorgosterol having a 25-ene side chain [Ten polyhydroxylated steroids were isolated from de chain .S. trocheliophorum yielded 9,11-secosteroid named, 25(26)-dehydrosarcomilasterol 416 and three polyhydroxylated steroids, 7α- hydrocrassorosterol A 417, 11α-acetoxy-7α-Hydrocrassorosterol A 418, sarcomilasterol 419, 3β,6α,11-trihydroxy-9,11-seco-5α-cholest-7-ene-9-one 420 and 3β,6α,11-trihydroxy-24-methylene-9,11-seco-5α-cholest-7-ene-9-one 421. The 9,11-secostroids nucleus can be described as the chemotaxonomic indicators for genus Sarcophyton [Ethanol-soluble fraction of the acetone extract of cophyton .S. glaucum, 16-deacetylhalicrasterol B 422, together with sarcoaldesterol B 396, sarglaucsterol 423 were isolated too and their structures were elucidated by spectral data [S. ehrenbergi the isolation of two formerly isolated hippurine 424 and 425 [426 were reported [Sacrophyton sp.Beside the abovementioned isoprenoids obtained from ral data . Further and 425  alongsidreported . Figure S. trocheliophorum, tetradecyl octadecenoate 427, 2,3-dihydroxypropyloctadecyl ether 428 and tetradecyl-9-Z-octadecenoate 429 were identified [S. trocheliophorum provided four butenolides 430–433 with different chain substitutions and saturation together with three fatty acids, arachidonic acid, eicosapentaenoic and docosahexaenoic methyl esters 434–436 and prostaglandin PGB2 437 [From PGB2 437 .S. crassocaule, (5Z)-9,15-dioxoprosta-5,8(12)-dien-1-oate 438 based on spectral analysis. This was the first time to report a prostaglandin with a C-15 keto group from natural origin [S. crassocaule, two isolated metabolites identified as sarcophytonone 439 a tetra-substituted quinone, and sarcophytonamine 440 a quaternary amine were reported. It might be valuable to know that these quinone derivatives are scarce in marine organisms and only sarcophytonone 439 was identified in S. mayi [An infrequent prostaglandin was isolated from l origin . Further S. mayi .S. infundibuliforme, three were reported O-glycosylglycerol known as sarcoglycosides A–C 441–443 and chimyl alcohol and hexadecanol 444 and 445. Sarcoglycoside A 441 was the first glycoglycerolipid to be isolated from soft coral, while sarcoglycosides B and C 442 and 443 were rare marine isolates, composed of a lyxose residue and chimyl alcohol moiety [S-3,11,14-trihydroxy-3,7,11,15-tetramethylhexadecylcyclohexa-2,5-diene-1,4-dione 446, was isolated [Five compounds were isolated from l moiety . Moreoveisolated .S. ehrenbergi yielded ten prostaglandins, sarcoehrendin A−J 447–456 together with five correlated compounds 457–461. Sarcoehrendin A 447 was found to be the acetylated derivative of arachidonic acid ethyl; previously isolated from Lobophyton depressum [462–467, were reported from S. ehrenbergi, three were reported to be of marine origin [S. ehrenbergi extract, 2-methyl-1-octanol ester of (E)-3-(4methoxyphenyl) propenoic acid 468 was reported. The authors mentioned that stereochemical structure of 2-methyl-1-octanol ester of (E)-3-(4methoxyphenyl) propenoic acid 468 was ensured via synthesis of two possible isomers (S)-1 and (R)-1 which was recognized by an asymmetric synthesis using 4-benzyl-2-oxazolidinone chiral auxiliaries from octanoic acid [S. ehrenbergi ceramide 469 was reported alongside two cerebrosides, sarcoehrenosides A and B 470 and 471. A detailed spectral analysis revealed the occurrence of an amide linkage, a long chain, and a sugar, dependable with the C-9 methyl cerebroside nature of sarcoehrenoside A 470 [Purification of ethyl acetate extract of epressum ,127. Anoe origin . From S.oic acid . From S.de A 470 .472–474 were reported for the first time from S. elegans. Chemical structures were interpreted by using spectral data and reported data [Sarcophyton sp. another carotenoid, all-trans---pyrrhoxanthin 475 was isolated [Three carotenoids, peridinin, peridininol and peridininol-5,8-furanoxide ted data . Additioisolated .476 and 477, two tetracyclic tetraterpenoids, together with methyl sartortuoate 478 and methyl isosartortuoate 479, were reported from S. tortuosum. Methyl tortuoate A 476 was similar to methyl sartortuoate 478 in structure, except for the presence of secondary hydroxyl group in methyl tortuoate A 476 and absence of one tertiary hydroxyl functional group and conjugated diene. As for, methyl tortuoate B 477, it was found to be similar to methyl isosartortuoate 479 in structure, but with no hydroxyl group at C-27 [480 after further investigation of the same ethanolic extract of S. tortuosum was isolated and a full spectral data was done to investigate its structure [481, was also reported from S. tortuosum and was identified using direct infusion electrospray ionization mass spectrometry [Sacrophyton sp.Methyl tortuoate A and methyl tortuoate B  at C-27 . Tetratetructure . Anothertrometry . Figure 9 was investigated, as a cytotoxic agent against gastric carcinoma using MTT method, colony formation method, cell morphology assessments, and wound-healing method. It suppressed the development and migration of gastric cancer cells in a dose-dependent manner and initiated both early and late cell death examined by flow cytometer assay [76, 77, 79, and 80, and emblide 81, and its activity, showing that loss of acetoxy group as in crassocolide C 84 led to loss of activity against all tested cell lines. While, acetylation at 4-OH position in crassocolide B 83 resulted in a decrease in activity cytotoxicity. However, the existence of two hydroxy moiety present at carbon-3 and carbon-4 and no oxidation at carbon-13 as in crassocolide D 85 showed potent activity against MCF-7 and A549 cell lines. While, crassocolide A 82 and F 87 exhibited potent activity toward Hep G2, MCF-7, MDA-MB-231 and A549, because of the 5-O-acetyl group [90 and 94, from S. crassocaule, showed strong activity toward KB, Hela, and Daoy cell lines owing to the presence of Cl atom at C-11 instead of OH group in crassocolide H 90 [The capability of 13- Acetoxysarcocrassolide er assay . The autyl group . Furtheride H 90 .137–140, showed potent activity toward MCF-7, WiDr, HEp-2 and Daoy cell lines [143–146, showed cytotoxicity toward all or part cell lines. However, sarcocrassocolide I 146 was most potent toward Daoy, HEp-2, MCF-7 and WiDr cell lines while sarcocrassocolide J and L 147 and 149 13-deacetoxy derivatives, were least potent against all tested cell lines with ED50 = >20 μM. Furthermore, hydroxy moiety at carbon-8 improve the cytotoxic activity in contrast with carbon-8 hydroperoxy-bearing correspondents sarcocrassocolide F and H 143 and 145 were most potent toward MCF-7 [Sarcocrassocolides A–D ll lines . The autrd MCF-7 .329 and 330 both exhibited strong cytotoxicity toward HL-60 and CCRF-CEM cell [71 was the most potent even better than the positive control Cyclosporin A [S)-24-methylcholestane-3β,5α,6β,25-tetrol-25-monoacetate 375 exhibited potent activity toward P-388, A549, and HT-29 cell lines [E-ene-3β,5α,6β,20(S)-tetraol 374, and acetyl group at C-25 position in 24-methylcholestane-3β,5α,6β,25-tetraol 25-monoacetate 375 led to strong cytotoxicity toward human M14, HL60, and MCF7 cells with a dose-dependent manner [R,24R,17Z)-11α-acetoxy-16β-methoxy-23,24-dimethylcholest-17(20)-en-3β,5α,6β-triol 406, -11α-acetoxy-ergost-22, 25-dien-3β,5α,6β-triol 411 and (24R)-11α-acetoxy-gorgost-3β,5α,6β-triol 413 showed a strong cytotoxicity toward K562, HL-60, HeLa cell lines, while, 11α-acetoxycholest-24-en-1α,3β,5α,6β-tetraol 408, 11α-acetoxy-cholest-24-en-3β,5α,6β-triol 410 and (24S)-11α-acetoxy-ergost-3β,5α,6β-triol 412 exhibited a potent activity toward K562 and HL-60 [Owing to the α,β-unsaturated ε-lactone ring in glaucumolides A and B CEM cell . The autsporin A . (24S)-2ll lines . The autnd HL-60 .150 could be a leading anti-inflammatory. Sarcocrassocolides M–O 150–152 might be beneficial anti-inflammatory agents because of the structure relationship and the existence of β-hydroperoxy moiety at carbon-7 [137–143 activity was attributed to the ring-opening of the α,β-unsaturated-β-ether ketone group leading to an increase in the enzyme inhibitory activity [310, 311, and 313 and ehrenbergol D 251 showed significant TNF-α inhibition in which sarcoehrenolide B 311 was most active due to the existence of acetoxy at carbon-18. A structure activity relationship was demonstrated in which the keto moiety at carbon-13 and hydroxyl group at carbon-18 could be responsible for the slight increase in activity. However, the presence of carbomethoxy moiety at carbon-18 led to a reduction in activity [Sarcocrassocolide M carbon-7 . Sarcocractivity . Sarcoehactivity .173 has strong inhibitory activity toward PTP1B because of the hydroperoxide group which binds to the active site of the Cys residue [50 and sarcrassin E 80 may be because of the existence of methyl ester moiety at carbon-18, which significantly increases the enzyme inhibitory activity toward human PTP1B enzyme [Methyl sarcotroate B  residue . PotencyB enzyme .32 showed a strong antibacterial activity toward methicillin-sensitive S. aureus Newman strain because of the diene at C-1/C-3 [231, 232, 235, 237, 238, and 241, 4-epi-sarcophytol L 243 showed antibacterial activity toward Xanthomonas vesicatoria, Agrobacterium tumefaciens, Pseudomonas lachrymans, Bacillus subtilis, and Staphylococcus aureus. The authors mentioned that the structure activity relationship and the existence of exomethylene group at C-8 add to the antibacterial activity, while H-3β orientation, which was present only in compound trocheliophol S 242, gave the most potent activity against the selected bacteria [430–433 were evaluated by using shrimp bioassay, and bioactivity was shown. Additionally, they showed activity against Gram-positive bacteria only [Sarcophytolide  C-1/C-3 . The cru C-1/C-3 . Trochelbacteria . The toxria only .384, -11α-acetoxy-ergostane-22,25-dien-3β,5α,6β-triol 385, 11α-acetoxy-gorgostane-3β,5α,6β,12α-tetraol 389, 12α-acetoxy-gorgostane-3β,5α,6β,11α-tetraol 390, and sarcoaldosterol A 391 were more potent toward antibacterial activity toward Escherichia coli and Bacillus megaterium, and antifungal activity toward Microbotryum violaceum and Septoria tritici fungi, because of the 11α-acetoxy group, cyclopropane side chain and terminal-double bond [Because of the structure activity relationship, 11α-acetoxy-cholesta-24-en-3β,5α,6β-triol ble bond .469, measured in vivo by the pentylenetetrazole (PTZ)-induced seizure assay, has successfully opposed the lethality of pentylenetetrazole in mice. It showed also a significant anxiolytic activity when used in the light–dark transition box. This could be caused possibly by GABA and serotonin receptors modulation [.Sacrophyton.Anticonvulsant activity of ceramide dulation .Table 1Sarcophyton species. The chemical structures were classified as terpenoids (majority), biscembranes, polyhydroxylated sterols, sesquiterpenes (minority), and miscellaneous compounds. S. trocheliophorum gave the highest number of compounds. Members of genus Sarcophyton possessed valuable and interesting biological activities, such as antibacterial, cytotoxicity, antifungal, and antidiabetic.Based on reviewing the available current literature, a huge library of metabolites was isolated, and it possessed unique structures. Up to 481 compounds with different structures belonging to different chemical classes were reported from the


Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds.In traditional Malay medicine, M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL).The most active dichloromethane extract of 1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin ( Marantodes pumilum (Blume) Kuntze belongs to the Primulaceae family + ; 1H-NMR  δH (ppm): 2.45 , 2.65 , 3.89 , and 6.91 ; 13C-NMR  δC (ppm): 162.7 (C-1), 157.1 (C-3), 139.9 (C-4), 110.2 (C-4a), 153.1 (C-5), 101.8 (C-6), 142.5 (C-7), 119.8 (C-8), 131.1 (C-8a), 18.2 (C-9), and 15.2 (C-10).The fraction CC1-F15 (0.69 g) was fractionated using Sephadex LH-20 column chromatography with 1% methanol in chloroform to yield eight fractions. The third fraction was then eluted using silica gel column chromatography with chloroform-methanol (9:1) to obtain five fractions. The fourth fraction was triturated with hexane–methanol (1:1) to give compound 2. Compound 2 was obtained as a yellow powder (5.0 mg), and the data for its structural elucidation were as follows: UV (EtOH) λmax nm (log ε): 285 (3.15), and 206 (3.00); IR (ATR) ʋmax, cm− 1: 3346, 3342, 2923, 2954, 1633, 1595, 1463, 1311, 1202, 1078, and 838; HR-ESI-MS (+ve mode) m/z: 527.4275 [M-H]+ ; 1H-NMR  δH (ppm): 1.29 , 1.47 , 2.02 , 2.46 , 3.88 , 5.35 , 5.86 , and 7.28 ; 13C-NMR  δC (ppm): 22.6 , 27.2 , 27.9 , 29.2–29.7 , 129.7 , 182.8 , 151.5 , 119.1 , 181.7 , 161.1 , and 102.2 .The fraction CC1-F3 (0.62 g) was fractionated using Sephadex LH-20 column chromatography with 1% methanol in chloroform to yield eight fractions. The fourth fraction was then eluted using silica gel column chromatography with chloroform-ethyl acetate (9:1), followed by trituration with hexane-methanol (1:1) to obtain compound 3. Compound 3 was obtained as a yellow crystal (10.0 mg), and the data for its structural elucidation were as follows: UV (EtOH) λmax nm (log ε): 285 (3.17) and 206 (2.97); IR (ATR) ʋmax, cm− 1: 3342, 2851, 2921, 1659, 1607, 1464, 1383, 1311, and 1200; HR-ESI-MS m/z: 363.5800 [M + H]+ ; 1H-NMR  δH (ppm): 0.93 , 1.29–1.34 , 1.45 , 2.05 , 2.41 , 3.85 , 5.36 , and 5.91 ; 13C-NMR  δC (ppm): 13.1 (C-15′), 21.9 (C-1′), 22.3–31.5 , 26.7 , 129.4 , 182.2 (C-1), 154.5 (C-2), 118.7 (C-3), 183.0 (C-4), 160.5 (C-5), 55.8 (OCH3), and 102.6 (C-6).The fraction CC1-F7 (2.0 g) was fractionated using Sephadex LH-20 column chromatography with 1% methanol in chloroform to yield ten fractions. The fifth fraction was purified by re-crystallization in methanol to yield compound 4. Compound 4 was obtained as a white needle crystal (14.0 mg), and the data for its structural elucidation were as follows: mp 133–134°C; UV (EtOH) λmax nm (log ε): 202 (3.76); IR (ATR) ʋmax, cm− 1: 3347, 2934, 2868, 1464, 1382, 1048, and 968; HR-ESI-MS m/z: 413.2666 [M + H]+ ; 1H-NMR  δH (ppm): 0.72 , 0.82 , 0.83 , 0.87 , 0.95 (H-9), 1.01 , 1.03 (H-14), 1.04 , 1.08 (H-15), 1.10 (H-1), 1.13 (H-17), 1.19 , 1.28 (H-16), 1.43 (H-28), 1.48 (H-8), 1.50 (H-7), 1.52 , 1.53 (H-25), 1.54 (H-24), 1.58 (H-15), 1.73 (H-16), 1.86 (H-2), 1.88 (H-1), 1.98 (H-7), 2.01 (H-12), 2.07 (H-20), 2.26 (H-4), 2.32 (H-4), 3.55 (H-3), 5.04 , 5.17 , and 5.37 (H-6); 13C-NMR  δC (ppm): 11.9 (C-18), 12.3 (C-29), 19.0 (C-27), 19.4 (C-19), 21.1 , 23.1 (C-21), 24.3 (C-15), 26.0 (C-28), 29.1 (C-16), 31.7 , 31.9 , 36.2 (C-10), 37.3 (C-1), 39.7 (C-12), 40.6 (C-20), 42.3 (C-13), 45.8 (C-4), 50.1 (C-9), 51.3 (C-24), 56.0 (C-17), 56.8 (C-14), 71.8 (C-3), 121.8 (C-6), 129.3 (C-23), 138.4 (C-22), and 140.8 (C-5).The fraction CC1-F1 (0.12 g) was precipitated to obtain compound 5. Compound 5 was obtained as a white waxy solid (10.8 mg), and the data for its structural elucidation were as follows: UV (EtOH) λmax nm (log ε): 202 (1.35); IR (ATR) ʋmax, cm− 1: 2915, 2849, 1473, 1463, 1262, 1021, 1096, 802, 729, and 719; HR-ESI-MS m/z: 338.3369 [M+] ; 1H-NMR  δH (ppm): 0.88 , 1.27 , and 1.32 .The fraction CC1-F10 (1.84 g) was fractionated using Sephadex LH-20 column chromatography with 1% methanol in chloroform to yield ten fractions. The fourth fraction was then eluted using silica gel column chromatography with chloroform-ethyl acetate (4:1) to obtain ten more fractions. The fourth fraction was further purified using silica gel column chromatography with chloroform-ethyl acetate (3:1) to obtain compound 6. Compound 6 was obtained as a white amorphous solid (9.0 mg), and the data for its structural elucidation were as follows: UV (EtOH) λmax nm (log ε): 202 (2.47); IR (ATR) ʋmax, cm− 1: 2916, 2848, 1706, 1697, 1463, 1430, 1411, 1310, 1295, 1272, 1251, 1229, 1208, 1188, 939, and 720; EI-MS m/z: 269 [M-1]+ ; 1H-NMR  δH (ppm): 0.89 , 1.26–1.32 , 1.65 , and 2.35 ; 13C-NMR  δC (ppm): 14.2 (C-17), 22.7 (C-16), 24.7 (C-3), 29.1–31.9 (C-4-C-15), 34.1 (C-2), and 180.3 (C-1).The fraction CC1-Fn = 3). The difference between means was determined at 95% confidence intervals, with p value < 0.05 considered as significantly different.Assay data obtained were subjected to one-way ANOVA with post-hoc Tukey’s multiple comparisons test using GraphPad Prism 5 software . The data are expressed as mean ± standard error of the mean (S.E.M.) with triplicate measurements . They were the dichloromethane extracts of var. alata , var. pumila , and var. lanceolata  leaves, and the methanol extracts of var. pumila  and var. lanceolata  leaves , 1734 (C=O), 1473–1424 (C-H bending), and 1256 (C-O stretching) cm− 1. Its 1H-NMR spectrum  showed methyl protons at δ 2.45  and δ 2.65 , a methoxy proton at δ 3.89 , and an aromatic proton at δ 6.91 (s). Its 13C-NMR spectrum  showed 12 carbons with signals indicating the presence of one carbonyl carbon at δ 162.7 (C-1), one methoxy carbon at δ 153.1 (C-5), and two methyl carbons at δ 18.8 (C-11) and δ 15.2 (C-12). Its 1H-1H COSY spectrum displayed the correlation between aromatic protons at δ 6.91 (s) and methoxy protons at δ 3.89, thus revealing the location of the aromatic proton group at the C-6 position. Its HSQC spectrum showed correlations between methoxy protons at δ 3.89 and δ 56.6 (C-5), an aromatic proton at δ 6.9 and δ 101.8 (C-6), and two methyl protons at δ 2.45 and δ 2.65 and δ 18.8 (C-9) and δ 15.2 (C-10), respectively. In its HMBC spectrum, the linkage of two methyl protons was established by the cross peaks between H-9 (δ 2.45) and C-4 , C-4a , and C-3 , and between H-10 (δ 2.65) and C-7 , C-8 , and C-8a . This correlation confirmed the position of methyl protons in compound 1. The spectrum also showed the correlation between methoxy protons at δ 3.89 and C-5 , and the correlation between aromatic protons (δ 6.91) and C-5 , C-7 , and C-8 . Therefore, based on the data above the structure of compound 1 was determined as 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin  [3) [4) [5) [6) [The other five known compounds were identified as ardisiaquinone A (2) , maesani2) [3) , stigmas [3) [4) , tetraco [4) [5) , and mar [5) [6)  1) and ardisiaquinone A (2) exhibited more than 50% xanthine oxidase inhibition (Table 1) being more potent than the latter (2). The former (1) had an IC50 value of 0.66 ± 0.01 μg/mL, which is comparable (p > 0.05) with that of allopurinol (IC50 = 0.24 ± 0.00 μg/mL) . The compound had an IC50 value (0.66 ± 0.01 μg/mL) that was comparable to that of allopurinol (IC50 = 0.24 ± 0.00 μg/mL) and could be a potential xanthine oxidase inhibitor. A study by Lin et al. [1) could explain the basis of its xanthine oxidase inhibitory activity. Another study also reported that the xanthine oxidase inhibitory activity of 5,7-dihydroxy-3-(3-hydroxyphenyl) coumarin was 7-fold better than that of allopurinol [2) and lack of activity of the other isolated compounds (3–6) obtained in this study could be explained by the difference in molecular structure that influences the stability of hydrophilic and hydrophobic characteristics on the xanthine oxidase active binding site [In this study, a new compound  was isolated from the dichloromethane extract of n et al.  demonstropurinol . The lowing site .M. pumilum extract to alleviate postmenopausal conditions due to estrogenic properties [M. pumilum var. pumilum could be beneficial in preventing or treating hyperuricemic-related diseases, while 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1) could be used as an analytical marker to standardize the extract and formulated herbal products. Standardization by simultaneous quantification of xanthine oxidase inhibitors from Zanthoxylum armatum fruits using high-performance liquid chromatography with a photometric diode array detector (HPLC-PDA) has been reported [There are several reviews on the anti-hyperuricemic effects of foods , Chineseoperties –60, hypeoperties , and hypoperties . Thus, treported .M. pumilum were investigated based on their ethnomedical uses and biological activities. The study identified a new isocoumarin compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), from the dichloromethane extract of M. pumilum var. pumila leaves. The compound was the most active xanthine oxidase inhibitor and had an IC50 value (0.66 ± 0.01 μg/mL) that was comparable with that of allopurinol (IC50 = 0.24 ± 0.00 μg/mL). Therefore, M. pumilum var. pumila leaves could potentially be a source of new natural xanthine oxidase inhibitors. However, in vivo studies are required to establish its efficacy and safety.In the present study, three varieties of


Canna edulis Ker rhizome has been used in Traditional Vietnamese Medicine to prevent and treat heart diseases without thorough scientific evidence. The data presented in this article characterize the antiplatelet aggregation, anticoagulant and antioxidant activity of C. edulis rhizome extracts and the bio-guided isolation of bioactive compounds from the active fraction. The data on tested bioactivities of isolated compounds were also provided. The inhibitory effect on adenosine diphosphate- and collagen-induced human platelet aggregation was evaluated through three parameters: percentage inhibition of platelet aggregation, aggregation velocity and area under the platelet aggregation curve. Prothrombin time, activated partial thromboplastine time and thrombine time were measured to examine the anticoagulant activity. The free radical scavenging ability was assessed with DPPH and ABTS assays. The structures of compounds were elucidated by NMR and MS spectroscopic methods. The data showed that the ethyl acetate fraction showed the most potent antiplatelet aggregation, anticoagulant and antioxidant activity. Seven known compounds: 5-hydroxy-6-methyl-2H-pyran-2-one (1), epimedokoreanone A (2), nepetoidin B (3), ferulic acid (4), caffeic acid (5), hydroxytyrosol (6), and 1H-indole-3-carboxaldehyde (7) were isolated from this active fraction. Moreover, this article provided experimental data on antiplatelet effect of epimedokoreanone A (2) and nepetoidine B (3), anticoagulant and antioxidant activity of epimedokoreanone A (2) and also antiplatelet and antioxidant activity of 5-hydroxy-6-methyl-2H-pyran-2-one (1). Specifications Table•C. edulis rhizome and its secondary metabolites.The data provide scientific evidences on antiplatelet aggregation, anticoagulant and antioxidant activity of •in-vitro and in vivo research to identify bioactive molecules with antiplatelet, anticoagulant and antioxidant activity from C. edulis rhizome, clarify mechanisms of action and develop new anti-thrombosis and antioxidant agents.This article can help in further •C. edulis rhizome and its secondary metabolite in this article also demonstrate the potential use of this edible plant to develop functional food for treatment and prevention of heart- and oxidative stress- related diseases.The reported bioactivities of •Canna edulis could be useful for the analysis of spectra and determination of the structure of isolated compounds from other Canna species.The provided information on the spectroscopic data of isolated compounds from •This data can serve as benchmark for other researchers to elucidate the structures of caffeic derivatives.Value of the data1C. edulis Ker rhizome and its secondary metabolites (Canna edulis described in the research article 1–7 isolated from the ethyl acetate fraction of C. edulis rhizomes (1H NMR of 1–7 are shown in 13C NMR of 1–7 are shown in 1H–13C heteronuclear single quantum coherence (HSQC) of 1, 3 and 7 are shown in 1H–13C heteronuclear multi-bond correlation (HMBC) spectra of 1, 3 and 7 are shown in 1, 3–6 and 7 are shown in 1–7 are reported in the research article The data set presented in this article focus on the antiplatelet aggregation, anticoagulant and antioxidant activity of extracts from abolites  and 2. Trhizomes . The 1H NMR information of each compounds are described as below:5-Hydroxy-6-methyl-2H-pyran-2-one (1):1H NMR  δH ppm: 2.36 , 6.41 , 7.69 .13C NMR  δC ppm: 172.91 (C-2), 112.89 (C-3), 154.25 (C-4), 143.12 (C-5), 148.67 (C-6), 14.26 (6-CH3).m/z: 127.2 [M + H]+APCI-MS positive 1 are shown in 1D NMR, 2D NMR, and APCI-MS of the compound Epimedokoreanone A (2):1H NMR  δH ppm: 2.33 , 7.80 13C NMR  δC ppm: 168.76 (C-2), 139.08 (C-3), 144.27 (C-4), 150.60 (C-5), 141.53 (C-6), 13.95 (6-CH3).1H and 13C NMR of the compound 2 are shown in Nepetoidin B (3):1H NMR  δH ppm: 7.14 , 6.83 , 7.05 , 7.74 , 6.46 , 7.30 , 6.77 , 6.93 , 5.64 , 7.24 .13C NMR  δC ppm: 127.63 (C-1), 115.56 (C-2), 146.89 (C-3), 150.09 (C-4), 116.59 (C-5), 123.37 (C-6), 148.89 (C-7), 113.73 (C-8), 165.76 (C-9), 127.82 (C-1′), 117.35 (C-2′), 146.01 (C-3′), 146.01 (C-4′), 116.18 (C-5′), 122.73 (C-6′), 113.21 (C-7′), 132.96 (C-8′).m/z: 313.0 [M-H]−APCI-MS negative 3 are shown in 1D NMR, 2D NMR, and APCI-MS of the compound Ferulic acid (4):1H NMR  δH ppm: 7.19 , 6.82 , 7.07 , 6.32 , 7.58 , 3.91 .13C NMR  δC ppm: 127.91 (C-1), 111.75 (C-2), 149.38 (C-3), 150.44 (C-4), 116.34 (C-5), 123.48 (C-6), 146.61 (C-7), 116.48 (C-8), 171.12 (C-9), 56.47 (4–OCH3).m/z: 193.1 [M-H]−APCI-MS negative 4 are shown in 1D NMR, and APCI-MS of the compound Caffeic acid (5):1H NMR  δH ppm: 7.05 , 6.79 , 6.94 , 6.22 , 7.55 .13C NMR  δC ppm: 127.90 (C-1), 115.09 (C-2), 146.76 (C-3), 149.36 (C-4), 122.77 (C-5), 116.49 (C-6), 146.78 (C-7), 115.92 (C-8), 171.34 (C-9.m/z: 179.1 [M-H]− .APCI-MS negative Hydroxytyrosol (6):1H NMR  δH ppm: 6.67 , 6.69 , 6.54 , 3.69 , 2.68 .13C NMR  δC ppm: 131.81 (C-1), 116.32 (C-2), 144.61 (C-3), 146.13 (C-4), 117.08 (C-5), 121.22 (C-6), 39.64 (C-7), 64.58 (C-8).m/z: 153.0 [M-H]− .APCI-MS negative 6 are shown in 1D NMR, and APCI-MS of the compound 1H-indole-3-carboxaldehyde (7):1H NMR  δH ppm: 7.24 , 7.29 , 7.49 , 8.11 , 8.18 .13C NMR  δC ppm: 113.12 (C-7), 120.13 (C-3), 122.37 (C-4), 123.60 (C-5), 124.99 (C-6), 125.72 (C-9), 138.94 (C-8), 139.65 (C-2), 187.41 (C-10).m/z: 146.1 [M + H]+.APCI-MS positive 7 are shown in 1D NMR, 2D NMR and APCI-MS of the compound 22.1C. edulis Ker rhizome, identified by the plant researcher Thi Thanh Huong Le – Thai Nguyen University of Sciences, Thai Nguyen, Vietnam, was collected in Thai Nguyen province, Vietnam. A voucher specimen number CE.R.TN01 is deposited at Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology.2.2C. edulis rhizome (CE.R) (6.2 kg) was macerated in ethanol 96% at room temperature and the solvent was evaporated. The total ethanol extract (CE.R.Et) then was fractionated with n-hexane, ethyl acetate (EA) and water. The n-hexane extract , EA extract  and the aqueous extracts  were obtained and evaporated under vacuum and then stored at 4–6 °C for further use.The dry powder of 1H, 125 MHz for 13C). APCI-MS was carried out using a AGILENT 6120 mass spectrometer at the Institute of Marine Biochemistry, Vietnam Academy of Science and Technology.The isolation of compounds from CE.R.EA was reported in the research article 2.39/L in PRP.Blood from healthy volunteers aged 18 - 35, who did not take any drugs for 3 weeks and were fasting overnight, was collected. A complete blood count was measured before platelet aggregation and coagulation experiments to ensure they had normal blood cell counts. The venous blood taken was put into a 3.2% sodium citrate tube and then centrifuged at 500 rpm for 10 min to take platelet-rich plasma (PRP). Blood sample was also centrifuged at 3000 rpm for 10 min to take platelet-poor plasma (PPP). Platelets were counted under microscope, and the platelet count was adjusted to 250 ± 25 × 10I) was calculated as %I = X is maximum percentage aggregation of the negative control; Y is maximum aggregation percentage of the sample The platelet aggregation was done using the turbidimetric method 2.4First, 450 μL of PPP were mixed with 50 μL of plant extracts or pure compounds and the mixtures then were incubated at 37° for 5 min. Then, PT, APTT and TT were measured using Sysmex CS-2100i machine (Japan) following the previously described method 2.52.5.1sOD is an average optical density of the sample, cOD is an average optical density of the control. The sample concentrations needed for 50% inhibition of the radicals  were calculated.The DPPH assay was carried out in triplicate according to the previously described method with some modifications 2.5.2+ was prepared by mixing 7 mM ABTS solution with 2.45 mM potassium persulfate solution (ratio 1:1) and kept in the dark for 14–16 h at room temperature + solution at room temperature for 10 min. The absorbance was read at 734 nm using a Microplate spectrophotometer. Trolox at 50, 100, 200, 500 µg/mL were used as the positive control. IC50 values were also calculated as described above. The experiment was done in triplicate.The working solution ABTSThe study was carried out in accordance with Declaration of Helsinki for experiments involving humans. Informed consent was obtained for experimentation with human subjects.The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.