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烯酰基酰基还原酶(InhA)抑制剂的研发:一篇综述短文

Development of Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review.

作者信息

Tailor Navin Kumar, Deswal Geeta, Guarve Kumar, Grewal Ajmer Singh

机构信息

University Institute of Pharma Sciences, Chandigarh University, Gharuan, Mohali, Punjab, India.

Department of Pharmacy, Guru Gobind Singh College of Pharmacy, Yamuna Nagar, 135001, Haryana, India.

出版信息

Mini Rev Med Chem. 2025;25(3):219-233. doi: 10.2174/0113895575309785240902102421.

Abstract

This review article delves into the critical role of Enoyl acyl carrier protein reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

摘要

这篇综述文章深入探讨了烯酰基载体蛋白还原酶(InhA;ENR)的关键作用,它是NADH依赖性酰基载体蛋白还原酶家族中的一种重要酶,强调了其在脂肪酸合成,更具体地说是在分枝菌酸生物合成中的重要性。这篇文献综述的主要目的是阐明针对InhA抑制的各种支架及其开发进展,从而破坏分枝菌酸的生物合成。已经系统地探索了包括硫脲、哌嗪、噻二唑、三唑、喹唑啉、苯甲酰胺、若丹宁、苯并恶唑和吡啶在内的各种支架作为InhA抑制剂的潜力。值得注意的发现突出了噻二唑和三唑衍生物,在纳摩尔浓度范围内显示出有前景的IC50值。该综述提供了关于InhA的结构、构效关系的全面见解,以及作为InhA有效抑制剂的不同支架的详细概述。

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