Latif_2021_Drug.Dev.Res_82_207

A series of new heterocycles (4-18) was synthesized by the structural modification of benzimidazole-2-thiol (BT, 2-MBI). The structures of the synthesized compounds were confirmed with the help of high-resolution mass spectrometry (HRMS) and (1) HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC(50) (s) = 167.4 microM (ABTS), 139.5 microM (DPPH)], 10 [IC(50) (s) = 186.5 microM (ABTS), 155.4 microM (DPPH)], 11 [IC(50) (s) = 286.1 microM (ABTS), 189.1 microM (DPPH)], 12 [IC(50) (s) = 310.8 microM (ABTS), 162.2 microM (DPPH)], 14 [IC(50) (s) = 281.3 microM (ABTS), 205.7 microM (DPPH)], 15 [IC(50) (s) = 284.1 microM (ABTS), 177.3 microM (DPPH)], and 16 [IC(50) (s) = 344.7 microM (ABTS), 270.2 microM (DPPH)] as compared with Ascorbic acid [IC(50) (s) = 340.9 microM (ABTS), 164.3 microM (DPPH)]. The anti-Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC(50) (s) = 121.2 microM (AChE), 38.3 microM (BChE)] as against that of galantamine [IC(50) (s) = 139.4 microM (AChE), 40.3 microM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC(50) = 35.4 microM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity.