Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines.
The anti-cancer property of curcumin, an active component of turmeric, is limited due to its poor solubility, stability and bioavailability. To enhance its efficacy, we designed a novel series of twenty-four monocarbonyl curcumin analogue-1,2,3-triazole conjugates and evaluated their anti-cancer activity towards endocrine related cancers. The new compounds (17-40) were synthesized through CuAAC click reaction and SAR analysis carried out. Out of these all, compound 17 showed most significant anti-cancer activity against prostate cancer cells with IC50 values of 8.8μM and 9.5μM in PC-3 and DU-145 cells, respectively. Another compound 26 showed significant anti-cancer activity against breast cancer cells with IC50 of 6μM, 10μM and 6.4μM in MCF-7, MDA-MB-231 and 4T1 cells, respectively while maintaining low toxicity towards non-cancer originated cell line, HEK-293. Compounds 17 and 26 arrested cell cycle and induced mitochondria-mediated apoptosis in cancer cells. Further, both of these compounds significantly down-regulated cell proliferation marker (PCNA), inhibited activation of cell survival protein (Akt phosphorylation), upregulated pro-apoptotic protein (Bax) and down-regulated anti-apoptotic protein (Bcl-2) in their respective cell lines. In addition, in vitro stability, solubility and plasma binding studies of the compounds 17 and 26 showed them to be metabolically stable. Thus, this study identified two new curcumin monocarbonyl-1,2,3-triazole conjugate compounds with more potent activity than curcumin against breast and prostate cancers.
['Mandalapu|Dhanaraju|D|', 'Saini|Karan S|KS|', 'Gupta|Sonal|S|', 'Sharma|Vikas|V|', 'Yaseen Malik|Mohd|M|', 'Chaturvedi|Swati|S|', 'Bala|Veenu|V|', 'Hamidullah|||', 'Thakur|Subhadra|S|', 'Maikhuri|Jagdamba P|JP|', 'Wahajuddin|Muhammad|M|', 'Konwar|Rituraj|R|', 'Gupta|Gopal|G|', 'Sharma|Vishnu Lal|VL|']
D000970:Antineoplastic Agents D017209:Apoptosis D001943:Breast Neoplasms D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D049109:Cell Proliferation D057930:Click Chemistry D003474:Curcumin D015536:Down-Regulation D004354:Drug Screening Assays, Antitumor D005260:Female D057809:HEK293 Cells D006207:Half-Life D006801:Humans D008297:Male D053078:Membrane Potential, Mitochondrial D018809:Proliferating Cell Nuclear Antigen D011471:Prostatic Neoplasms D051057:Proto-Oncogene Proteins c-akt D019253:Proto-Oncogene Proteins c-bcl-2 D014230:Triazoles D051028:bcl-2-Associated X Protein
Hybridization Curcumin mimics 1,2,3-Triazole AKT-pathway Endocrine cancers