COX-2/DHODH双重抑制剂存在可行性的初步对接虚拟筛选研究

Feasibility study of the existence of dual inhibitors of COX-2/DHODH based on virtual screening

首次开展了探索环氧合酶-2(COX-2)和二氢乳清酸脱氢酶(DHODH)双重抑制剂存在的可行性研究工作。通过自建COX-2抑制剂数据库,采用虚拟筛选方法,以DHODH的晶体结构为靶标,对自建的COX-2抑制剂数据库进行对接虚拟筛选,筛选出多个对DHODH可能有抑制作用并且具有COX-2抑制活性的分子。研究表明,现有数据库中的25000系列、7000系列、26000系列以及33000系列的抑制剂最有可能成为DHODH和COX-2的双抑制剂,特别是其中的25002、7004和7006这三个抑制剂,具有进一步实验研究的价值。

A feasibility study of the existence of dual inhibitors of COX-2/DHODH has been explored for the first time. We constructed a database with inhibitor structures and activities （ IC50 or logl/C） using 773 inhibitors of COX-2. Based on the crystal structure of DHODH （PDB code： 1d3h）, virtual screening was performed against the constructed database. Taking into account docking energy and the molecular activities of COX-2, some compounds were selected. It was found that the inhibitors of series 25000, 7000, 26000 and 33000 are possible dual inhibitors of COX-2/DHODH and the compounds 25002, 7004, 7006, in particular, have potential value for real bioassays.