The Mycobacterium tuberculosis Cell Wall: An Alluring Drug Target for Developing Newer Anti-TB Drugs—A Perspective

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Chemical Biology & Drug Design Pub Date : 2024-09-05 DOI:10.1111/cbdd.14612
Monica Chauhan, Rahul Barot, Rasana Yadav, Karan Joshi, Sadaf Mirza, Rupesh Chikhale, Vijay Kumar Srivastava, Mange Ram Yadav, Prashant R. Murumkar
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Abstract

The Mycobacterium cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti-TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating Mtb infection.

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结核分枝杆菌细胞壁:开发新型抗结核药物的诱人药物靶点--透视。
分枝杆菌的细胞壁是一种胶囊状结构,由多层生物大分子组成,如霉菌酸、肽聚糖和阿拉伯半乳聚糖,它们为分枝杆菌提供了一种细胞防护。异烟肼、乙胺丁醇、环丝氨酸、delamanid 和 pretomanid 等药物通过抑制参与细胞壁合成的一种或另一种酶来抑制细胞壁的合成。这些层中存在的许多酶是设计和开发新型抗结核药物的潜在靶点。其中一些靶点目前正被作为最有药用价值的靶点加以利用,如 DprE1、InhA 和 MmpL3。目前临床试验中的许多抗结核药物都抑制细胞壁的合成。本文从系统的角度阐述了如何开发细胞壁抑制剂,将参与细胞壁生物合成的各种酶作为治疗 Mtb 感染的潜在候选药物。
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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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