Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

Author:

Acar Cevik Ulviye,Saglik Begüm,Levent Serkan,Osmaniye Derya,Kaya Cavuşoglu Betul,Ozkay Yusuf,Kaplancikli Zafer

Abstract

Alzheimer’s disease (AD), one of the main causes of aged dementia, is a progressive and degenerative neurological disorder characterized by loss of cognition and memory. Although the symptomatic treatment of AD, particularly acetylcholinesterase inhibitors (AChEIs) based on the ‘cholinergic hypothesis’, has been successful in clinic, at present there is no cure for this disease. In this study, we designed compounds carrying benzimidazole and triazole rings on the same chemical skeleton so as to investigate their potential acetylcholinesterase and butyrylcholinesterase activity. Furthermore, molecular modeling study was performed to determine the binding mode of the best inhibitor to the AChE. Among them, compounds 3d and 3h, which featured 3,4-dihydroxy substitution at the phenyl ring and 5(6)-chloro substitution at the benzimidazole ring were found to be potent inhibitors of AChE. The inhibition kinetics of the two most active derivatives 3d and 3h were further studied. The kinetic displayed increasing slope and increasing intercept, which is consistent with a mixed inhibition. The IC50 and Ki values of 3d are 31.9 ± 0.1 nM and 26.2 nM, respectively. Compound 3h exhibited IC50 of 29.5 ± 1.2 nM and Ki of 24.8 nM. The above data compared favorably with data for donepezil (21.8 ± 0.9 nM) the reference compound in our study.

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3