期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 40, 期 20, 页码 10278-10299出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2021.1942212
关键词
Acetylcholinesterase; butyrylcholinesterase; metal chelation; MTDL; carbazole; Alzheimer's disease
资金
- AICTE, New Delhi [ID-1-3526872437]
- DST-INSPIRE, New Delhi [IF-150660]
Carbazole-based derivatives were designed, synthesized, and evaluated for their inhibitory activity against cholinesterase, antioxidant properties, and metal chelating abilities. Two compounds showed promising ChE inhibitory activity and specific copper ion chelating ability, along with strong interactions with the active sites of ChE enzymes. These compounds also demonstrated significant in silico drug-like pharmacokinetic properties.
With the aim to combat a multi-faceted neurodegenerative Alzheimer's disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, (E)-2-((9ethyl-9H-carbazol-3-yl)methylene)-N-(pyridin-2-yl)hydrazinecarbothioamide (62) and (E)-2-((9-ethyl-9Hcarbazol-3-yl)methylene)-N-(5-chloropyridin-2-yl)hydrazinecarbothioamide (63) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 mM and 1.18 mM for hAChE, IC50 values of 2.69 mM and 3.31 mM for EqBuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62) and (63) were 85.67% and 84.49%, respectively at 100 mM concentration). Compounds (62) and (63) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62) and (63) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据