基于喜树碱的新型抗肿瘤药物的设计和虚拟筛选

Design and Virtual Screening of Novel Anticancer Drugs Based on Camptothecin

为研究喜树碱C11位衍生物对其抗肿瘤活性活性的影响,用于开发喜树碱家族新型抗肿瘤药物,本文以羟基喜树碱为先导化合物,设计了8类C11位修饰的化合物。通过MOE软件导入化合物构象,以人体DNA拓扑异构酶Ⅰ(PDB ID:1T8I)为受体靶点,进行分子对接,筛选出三个化合物3、4、5具有更高潜在的抗肿瘤活性,并对其相互作用进行分析,为喜树碱类抗肿瘤药物的设计及合成提供了新的参考。

In order to study the effect of C11 derivatives of camptothecin on its antitumor activity and develop new antitumor drugs of camptothecin family,eight kinds of C11 modified compounds were designed with hydroxycamptothecin as the lead compound.The conformation of the compound was introduced through MOE software,and the human DNA topoisomerase I(PDB ID:1T8I)was used as the receptor target for molecular docking.Three compounds 3,4 and 5 were screened out to have higher potential antitumor activity,and their interactions were analyzed,which provided a new reference for the design and synthesis of camptothecin antitumor drugs.