首页 > 中国药理学报（英文版） > Discovery of novel DprE1 inhibitors via computational bioactivity fingerprints and structure-based virtual screening

Discovery of novel DprE1 inhibitors via computational bioactivity fingerprints and structure-based virtual screening

导出原文传递学术成果认领

翻译打印收藏纠错

摘要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.

作者 Xue-ping Hu ^[1] Liu Yang ^[2] Xin Chai ^[2] Yi-xuan Lei ^[2] Shah Alam ^[3] Lu Liu ^[4] Chao Shen ^[2] De-jun Jiang ^[2] Zhe Wang ^[2] Zhi-yong Liu ^[3] Lei Xu ^[5] Kang-lin Wan ^[6] Tian-yu Zhang ^[3] Yue-lan Yin ^[7] Dan Li ^[2] Dong-sheng Cao ^[4] Ting-jun Hou ^[1] 学术成果认领

作者单位 Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;State Key Lab of CAD&CG,Zhejiang University,Hangzhou 310058,China ^[1] Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China ^[2] State Key Laboratory of Respiratory Disease,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;University of Chinese Academy of Sciences,Beijing 100049,China ^[3] Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China ^[4] Institute of Bioinformatics and Medical Engineering,School of Electrical and Information Engineering,Jiangsu University of Technology,Changzhou 213001,China ^[5] State Key Laboratory of Infectious Disease Prevention and Control,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China ^[6] Jiangsu Key Laboratory of Zoonosis,Yangzhou University,Yangzhou 225009,China ^[7]

关键词 molecular docking virtual screening DprE1 tuberculosis covalent inhibitors

栏目名称

Drug Discovery

发布时间 2022-07-21（万方平台首次上网日期，不代表论文的发表时间）

翻译满意度评价：

准确一般字义偏差语意偏离译文作用小提交