DprE1 小分子抑制剂的虚拟筛选

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.

Department of Computer Application, Shenyang Sport University, Shenyang 110102, China.

Molecules. 2018 Feb 27;23(3):524. doi: 10.3390/molecules23030524.

Decaprenylphosphoryl-β-d-ribose oxidase (DprE1) is the flavoprotein subunit of decaprenylphosphoryl-d-ribose epimerase involved in cell wall synthesis in and catalyzes the conversion of decaprenylphosphoryl ribose to decaprenylphosphoryl arabinose. DprE1 is a potential target against tuberculosis, including multidrug-resistant tuberculosis. We identified potential DprE1 inhibitors from the ChemDiv dataset through virtual screening based on pharmacophore and molecular docking. Thirty selected compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity prediction with the Discovery Studio software package. Two compounds were obtained as hits for inhibiting DprE1 activity in and are suitable for further in vitro and in vivo evaluation.

脱磷酸-D-核糖基-β-D-阿拉伯庚酮糖氧化酶（DprE1）是参与细胞壁合成的脱磷酸-D-核糖基阿拉伯庚酮糖异构酶的黄素蛋白亚基，它催化脱磷酸-D-核糖基向脱磷酸-D-阿拉伯庚酮糖的转化。DprE1 是针对结核分枝杆菌，包括耐多药结核分枝杆菌的潜在靶点。我们通过基于药效团和分子对接的虚拟筛选，从 ChemDiv 数据集鉴定出潜在的 DprE1 抑制剂。使用 Discovery Studio 软件包对 30 种选定的化合物进行吸收、分布、代谢、排泄和毒性预测。有两种化合物作为 DprE1 抑制剂的命中化合物被筛选出来，适合进一步进行体外和体内评估。