Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles.
Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC50 = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ± 0.09 µM, and IC50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.
['Rafique|Rafaila|R|', 'Khan|Khalid Mohammed|KM|', 'Arshia|||', 'Chigurupati|Sridevi|S|', 'Wadood|Abdul|A|', 'Rehman|Ashfaq Ur|AU|', 'Salar|Uzma|U|', 'Venugopal|Vijayan|V|', 'Shamim|Shahbaz|S|', 'Taha|Muhammad|M|', 'Perveen|Shahnaz|S|']
D006801:Humans D007191:Indazoles D062105:Molecular Docking Simulation D015394:Molecular Structure D000516:alpha-Amylases
In vitro Indazole α-amylase enzyme In silico ABTS and DPPH Sulfonohydrazide