Discovery of novel triple targeting G–quadruplex and topoisomerase 1/2 ligands from natural products evodiamine and rutaecarpine  

作　　者：Haibo Wang Xuexin Bai Yahui Huang Yueru Chen Guoqiang Dong Tianmiao Ou Shanchao Wu Defeng Xu Chunquan Sheng 

机构地区：[1]National&Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass,School of Pharmacy,Changzhou University,Changzhou 213164,China [2]Department of Medicinal Chemistry,School of Pharmacy,Second Military Medical University,Shanghai 200433,China [3]School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China

出　　处：《Chinese Chemical Letters》2023年第4期203-210,共8页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos. 22077138 to S. Wu, 81725020 to C. Sheng;81872742 to G. Dong);the National Key Research and Development Program of China (No. 2020YFA0509200 to C. Sheng);Shanghai Rising-Star Program (No. 22QA1411300 to S. Wu)。

摘　　要：Inspired by the indolopyridoquinazoline scaffold of natural products evodiamine and rutaecarpine, novel triple G4 and Top1/2 ligands were rationally designed and synthesized. Systematic structure–activity relationship(SAR) studies led to the discovery of compound 15g, which effectively induced and stabilized G4 and inhibited Top1/2 with potent antitumor activity. Compound 15g represents a valuable chemical tool or lead compound for antitumor drug discovery. This proof-of-concept study also validated the feasibility of using planar natural products scaffold as templates to design new G4 ligands.

关 键 词：Indolopyridoquinazoline G-QUADRUPLEX TOPOISOMERASE Structure-activity relationship Antitumor activity 

分 类 号：TQ460.1[化学工程—制药化工]