N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers:Design,structure-activity relationships and biological evaluations  

作　　者：Jian Song Shenghui Wang Qiuge Liu Xiao Wang Shuo Yuan Hongmin Liu Saiyang Zhang 

机构地区：[1]School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450001,China [2]School of Pharmaceutical Sciences,Institute of Drug Discovery&Development,Key Laboratory of Advanced Drug Preparation Technologies(Ministry of Education),Zhengzhou University,Zhengzhou 450001,China [3]State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou 450001,China [4]Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China

出　　处：《Chinese Chemical Letters》2025年第2期228-233,共6页中国化学快报(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.82273782 and U2004123);Training Program for Young Key Teachers of Colleges and Universities in Henan Province(No.2023GGJS008)。

摘　　要：In this work,we employed a ring-opening strategy to develop a series of novel N-benzyl arylamide derivatives as tubulin polymerization inhibitors.Notably,13n(MY-1388)exhibited remarkable antiproliferative potency on fifteen human cancer cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 8 nmol/L to 48 nmol/L.Furthermore,13n effectively suppressed tubulin polymerization by targeting the colchicine-binding site(IC_(50)=0.62μmol/L).13n also exhibited significant inhibition of cell colony formation,as well as displayed potent effects on inducing G2/M phase cell cycle arrest and promoting apoptosis.Importantly,13n exhibited enhanced and adequate liver microsomal stability in human and rat liver microsomes,and also exhibited a moderate half-life(T_(1/2)=0.938 h)in vivo.Meanwhile,13n demonstrated effective antitumor effects in vivo in suppressing tumor growth in the MGC-803xenograft model(tumor growth inhibition(TGI)value was 76.4%at the dosage of 30 mg kg^(-1)day^(-1))with a good safety profile.Collectively,these results revealed that 13n represents a promising tubulin polymerization inhibitor that deserves further investigation for its efficacy in treating gastric cancers.

关 键 词：TUBULIN Colchicine binding site CA-4 N-Benzyl arylamide Antiproliferative activities 

分 类 号：TQ245.27[化学工程—有机化工] R914[医药卫生—药物化学]