Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.
Chem Biol Drug Des. 2021 Jan;97(1):148-156. doi: 10.1111/cbdd.13769. Epub 2020 Aug 24.
Emergence of MDR-TB and XDR-TB led to the failure of available anti-tubercular drugs. In order to explore, identify and develop new anti-tubercular drugs, novel peptidomimetic series of Mtb-peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a, 4b, 4c, 4d, and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25 µg/ml against M. tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb-peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.
耐多药结核病（MDR-TB）和广泛耐药结核病（XDR-TB）的出现导致现有抗结核药物失效。为了探索、鉴定和开发新的抗结核药物，设计并合成了一系列新型的结核分枝杆菌肽脱甲酰基酶（PDF）抑制剂的肽模拟物。通过用 MABA 筛选化合物对结核分枝杆菌 H37Rv 株的抗分枝杆菌活性，确定了化合物的体外抗分枝杆菌潜力。其中，酯类化合物 4a、4b、4c、4d 和 4e 表现出最强的活性，化合物 4c 具有很高的活性，对 M. tb H37Rv 株的最小抑菌浓度为 6.25μg/ml。此外，还对这些化合物进行了对接，以确定可能的结合相互作用，并了解活性最强的分子对 Mtb-peptide deformylase (PDF) 的作用机制，PDF 参与分枝杆菌蛋白的合成。
