一氧化氮合酶
化学
对接(动物)
香豆素
苯并咪唑
一氧化氮
生物信息学
百里香科
立体化学
组合化学
体外
IC50型
生物化学
体内
药理学
铅化合物
生物活性
酶
生物
医学
生物技术
护理部
有机化学
基因
生态学
作者
Richa Minhas,Yogita Bansal
出处
期刊:Medicinal Chemistry
日期:2022-01-01
卷期号:18 (5): 602-615
被引量:2
标识
DOI:10.2174/1573406417666210927123137
摘要
Inducible nitric Oxide Synthase (iNOS) plays a key role in the progression of inflammatory diseases by accelerating the production of NO, which makes it an intriguing target to treat inflammation in complex diseases. Therefore, the search is on to develop molecules as selective iNOS inhibitors.The present work was aimed to design, synthesize and evaluate benzimidazole-coumarin coupled molecules as anti-iNOS agents through in silico and pharmacological studies.A critical study of literature reports on iNOS inhibitors led to the selection of a (un)substituted coumarin nucleus, 2-aminobenzimidazole, and a 4-atom linker as important structural components for iNOS inhibition. Two series of compounds (7-16 and 17-26) were designed and synthesized by coupling these components. The compounds were subjected to docking using iNOS (1QW4) and nNOS (1QW6) as targets. All compounds were evaluated for NO and iNOS inhibitory activities in vitro. The selected compound was finally evaluated for anti-inflammatory activity in vivo using the carrageenan-induced rat paw edema model.All compounds showed moderate to good inhibition of NO and iNOS in vitro. Compound 12 was the most potent inhibitor of NO and iNOS. Hence, it was evaluated in vivo for toxicity and anti-inflammatory activity. It was found to be safe in acute toxicity studies, and effective in reducing the rat paw edema significantly. Its anti-inflammatory behaviour was similar to that of aminoguanidine, which is a selective iNOS inhibitor.The newly synthesized benzimidazole-coumarin hybrids may serve as potential leads for the development of novel anti-iNOS agents.
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