Synthesis, α-glucosidase inhibition and antioxidant activity of the 7-carbo-substituted 5-bromo-3-methylindazoles.

Abstract Series of 7-aryl- (3a–f), 7-arylvinyl- (3g–k) and 7-(arylethynyl)-5-bromo-3-methylindazoles (4a–f) have been evaluated through enzymatic assay in vitro for inhibitory effect against α-glucosidase activity and for antioxidant potential through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 3a–k and 4a–f showed significant to moderate α-glucosidase inhibition with IC50 values in the range of 0.50–51.51 μM and 0.42–23.71 μM compared with acarbose drug (IC50 = 0.82 μM), respectively. 5-Bromo-3-methyl-7-phenyl-1H-indazole (3a), 5-bromo-3-methyl-7-styryl-1H-indazole (3h) and 5-bromo-3-methyl-7-styryl-1H-indazole (4a) exhibited moderate to significant antigrowth effect against the breast MCF-7 cancer cell line and reduced cytotoxicity against the human embryonic kidney derived Hek293-T cells when compared to doxorubicin as reference standard. Non-covalent (alkyl, π-alkyl and π-π T shaped), electrostatic (π-sulfur and/or π-anion) and hydrogen bonding interactions are predicted to increase interactions with protein residues, thereby enhancing the inhibitory effect of these compounds against α-glucosidase.