Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis

作     者：Wenbin Kuang Haolin Zhang Xiao Wang Peng Yang Wenbin Kuang;Haolin Zhang;Xiao Wang;Peng Yang

作者机构：State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and OptimizationChina Pharmaceutical UniversityNanjing 210009China Department of Medicinal ChemistrySchool of PharmacyChina Pharmaceutical UniversityNanjing 210009China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第8期

页      面：3201-3214页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by National Natural Science Foundation of China (82073701,31900687) Natural Science Foundation of Jiangsu Province (SBK2019040713,China) the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University (SKLNMZZ202013) supported by Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University (No.2020KFKT-5) “Double First-Class” University Project (CPU2018GF04,China) 

主　　题：Mycobacterium tuberculosis Small molecule inhibitor Cell wall synthesis Antibiotic resistance 

摘      要：Mycobacterium tuberculosis(MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotictolerant MTB infections. Although several inexpensive and effective drugs(isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.