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

作者机构：National&Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of BiomassSchool of PharmacyChangzhou UniversityChangzhou 213164China Department of Medicinal ChemistrySchool of PharmacySecond Military Medical UniversityShanghai 200433China School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第4期

页      面：203-210页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 0703[理学-化学] 10[医学] 

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)。 

主　　题：Indolopyridoquinazoline G-quadruplex Topoisomerase Structure-activity relationship Antitumor activity 

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.