| Literature DB >> 34667293 |
Xue-Ping Hu1,2, Liu Yang1, Xin Chai1, Yi-Xuan Lei1, Md Shah Alam3,4, Lu Liu5, Chao Shen1, De-Jun Jiang1, Zhe Wang1, Zhi-Yong Liu3,4, Lei Xu6, Kang-Lin Wan7, Tian-Yu Zhang3,4, Yue-Lan Yin8, Dan Li9, Dong-Sheng Cao10, Ting-Jun Hou11,12.
Abstract
Decaprenylphosphoryl-β-D-ribose oxidase (DprE1) plays important roles in the biosynthesis of mycobacterium cell wall. DprE1 inhibitors have shown great potentials in the development of new regimens for tuberculosis (TB) treatment. In this study, an integrated molecular modeling strategy, which combined computational bioactivity fingerprints and structure-based virtual screening, was employed to identify potential DprE1 inhibitors. Two lead compounds (B2 and H3) that could inhibit DprE1 and thus kill Mycobacterium smegmatis in vitro were identified. Moreover, compound H3 showed potent inhibitory activity against Mycobacterium tuberculosis in vitro (MICMtb = 1.25 μM) and low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. Our research provided an effective strategy to discover novel anti-TB lead compounds.Entities:
Keywords: DprE1; covalent inhibitors; molecular docking; tuberculosis; virtual screening
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Year: 2021 PMID： 34667293 PMCID： PMC9160271 DOI： 10.1038/s41401-021-00779-1
Source DB: PubMed Journal: Acta Pharmacol Sin ISSN： 1671-4083 Impact factor: 7.169