Mannich-Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study


ALPAN A. S. , Sarikaya G. , ÇOBAN G. , Parlar S. , ARMAGAN G. , ALPTÜZÜN V.

ARCHIV DER PHARMAZIE, vol.350, no.7, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 350 Issue: 7
  • Publication Date: 2017
  • Doi Number: 10.1002/ardp.201600351
  • Title of Journal : ARCHIV DER PHARMAZIE
  • Keywords: Antioxidant activity, Benzimidazole, Cholinesterase inhibitors, Mannich bases, Molecular modeling, KNOCK-OUT MICE, ALZHEIMERS-DISEASE, OXIDATIVE STRESS, 1H-BENZIMIDAZOLE DERIVATIVES, MULTIFUNCTIONAL AGENTS, GENETIC ALGORITHM, FORCE-FIELD, BUTYRYLCHOLINESTERASE, ACETYLCHOLINESTERASE, DESIGN

Abstract

A series of Mannich bases of benzimidazole derivatives having a phenolic group were designed to assess their anticholinesterase and antioxidant activities. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds exhibited moderate to good AChE inhibitory activity (except for 2a), with IC50 values ranging from 0.93 to 10.85 mu M, and generally displayed moderate BuChE inhibitory activity. Also, most of the compounds were selective against BuChE. Compound 4b was the most active molecule on the AChE enzyme and also selective. In addition, we investigated the antioxidant effects of the synthesized compounds against FeCl2/ascorbic acid-induced oxidative stress in the rat brain in vitro, and the activity results showed that most of the compounds are effective as radical scavengers. Molecular docking studies and molecular dynamics simulations were also carried out.