Diab Ahmad, Dickerson Henry, Al Musaimi Othman
School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.
Pharmaceuticals (Basel). 2025 Jan 9;18(1):70. doi: 10.3390/ph18010070.
infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in . This review provides a comprehensive analysis of these drugs and their molecular mechanisms. Isoniazid, thioamides, and delamanid primarily disrupt mycolic acid synthesis, with recent evidence indicating that delamanid also inhibits decaprenylphosphoryl-β-D-ribose-2-epimerase, thereby impairing arabinogalactan biosynthesis. Cycloserine remains the sole approved drug that inhibits peptidoglycan synthesis, the foundational layer of the mycobacterial cell wall. Furthermore, ethambutol interferes with arabinogalactan synthesis by targeting arabinosyl transferase enzymes, particularly embB- and embC-encoded variants. Beyond these, six promising molecules currently in Phase II clinical trials are designed to target arabinan synthesis pathways, sutezolid, TBA 7371, OPC-167832, SQ109, and both benzothiazinone derivatives BTZ043 and PBTZ169, highlighting advancements in the development of cell wall-targeting therapies.
感染仍然是一项重大的全球健康挑战，尤其是由于多重耐药菌株的增加、分枝杆菌的随机突变以及与短期抗生素治疗方案相关的并发症。目前，有五种获批药物靶向[细菌名称]中的细胞壁生物合成。本综述对这些药物及其分子机制进行了全面分析。异烟肼、硫代酰胺和地拉曼德主要破坏分枝菌酸合成，最近有证据表明地拉曼德还抑制癸酰磷酸基-β-D-核糖-2-表异构酶，从而损害阿拉伯半乳聚糖的生物合成。环丝氨酸仍然是唯一获批的抑制肽聚糖合成的药物，肽聚糖是分枝杆菌细胞壁的基础层。此外，乙胺丁醇通过靶向阿拉伯糖基转移酶，特别是embB和embC编码的变体，干扰阿拉伯半乳聚糖的合成。除此之外，目前处于II期临床试验的六种有前景的分子旨在靶向阿拉伯聚糖合成途径，即舒替唑胺、TBA 7371、OPC-167832、SQ109以及苯并噻嗪酮衍生物BTZ043和PBTZ169，这突出了细胞壁靶向疗法开发方面的进展。
