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 f...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.展开更多
A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggre...A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.展开更多
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)。
文摘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.
基金KZ acknowledges supports from the National Young Scholar Award of the NSFC(#30125043)from the Chung Kong Scholars Program administered by the Ministry of Education,PRC and the Li Ka Shing Foundation,Hong Kong.
文摘A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.
