Faculty of Pharmacy, Kalabhavan Campus, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
The Cambridge Crystallography Data Center, Cambridge, UK.
Chem Biol Drug Des. 2024 Sep;104(3):e14612. doi: 10.1111/cbdd.14612.
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.
分枝杆菌细胞壁是一种类似胶囊的结构,由各种生物分子组成,如分枝菌酸、肽聚糖和阿拉伯半乳聚糖,为分枝杆菌提供了一种细胞盾牌。异烟肼、乙胺丁醇、环丝氨酸、德拉马尼和丙硫异烟胺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合成。这些层中的许多酶可作为设计和开发新型抗结核药物的潜在靶标。其中一些靶标目前正被用作最适合药物开发的靶标,如 DprE1、InhA 和 MmpL3。许多临床试验中的抗结核药物都抑制细胞壁的合成。本文综述了针对细胞壁生物合成中各种酶的细胞壁抑制剂的开发,作为治疗 Mtb 感染的潜在药物候选物。