Department of Biochemistry, University of Delhi South Campus , New Delhi, India.
Microbiol Spectr. 2023 Dec 12;11(6):e0135923. doi: 10.1128/spectrum.01359-23. Epub 2023 Oct 19.
Non-compliance to lengthy antituberculosis (TB) treatment regimen, associated side effects, and emergence of drug-resistant strains of () emphasize the need to develop more effective anti-TB drugs. Here, we have evaluated the role of dihydrodipicolinate reductase (DapB), a component of the diaminopimelate pathway, which is involved in the biosynthesis of both lysine and mycobacterial cell wall. We showed that DapB is essential for the as well as intracellular growth of . We further utilized DapB, as a target for identification of inhibitors by employing virtual screening, and conducted various screening assays to identify inhibitors with potential to inhibit DapB activity and and intracellular growth of with no significant cytotoxicity against various mammalian cell lines. Altogether, DapB serves as an important drug target and a hit molecule, namely, 4-(3-Phenylazoquinoxalin-2-yl) butanoic acid methyl ester has been identified as an antimycobacterial molecule in our study.
不遵守冗长的抗结核 (TB) 治疗方案、相关副作用以及耐药菌株的出现（）强调需要开发更有效的抗 TB 药物。在这里，我们评估了二氢二吡啶羧酸还原酶 (DapB) 的作用，它是二氨基庚二酸途径的一个组成部分，参与赖氨酸和分枝杆菌细胞壁的生物合成。我们表明 DapB 对（）的生长以及细胞内生长是必需的。我们进一步利用 DapB 作为通过虚拟筛选识别抑制剂的靶标，并进行了各种筛选测定，以鉴定具有抑制 DapB 活性和（）以及对各种哺乳动物细胞系无明显细胞毒性的潜力的抑制剂。总之，DapB 是一个重要的药物靶点和命中分子，即 4-(3-苯基偶氮喹喔啉-2-基)丁酸甲酯已被确定为我们研究中的一种抗分枝杆菌分子。
