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
The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studie...The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studies focus on designing homogeneous or noble metal catalysts and conducting the reactions under basic conditions.Here,we report an efficient process for the C-C bond cleavage of lignin model compounds and selectively producing esters over different shaped CeO_(2)(i.e.,nanospheres(S),nanorods(R),nanoparticles(P),and nanocubes(C))under base-free conditions.Specifically,the yield of methyl anisate from the aerobic oxidation of l-(4-methoxyphenyl)ethanol reaches 77.6%over CeO_(2)-S in one hour(91%in 9 h),exhibiting higher performance compared to other evaluated CeO_(2)catalysts(6.4%-40.2%).Extensivecharacterizations and experimental investigations reveal that the density of weak base sites and oxygen vacancies on the CeO_(2)surface is positively correlated with the yield of methyl esters.Furthermore,the reaction pathway is investigated,which confirms that 1-(4-methoxyphenyl)ethanol first undergoes two reactions(i.e.,etherification and dehydrogenation)to produce intermediates of1-methoxy-4-(1-methoxy-ethyl)-benzene and 1-(4-methoxyphenyl)ethanone,respectively,followed by a series of functional group transformations to generate the targeted methyl anisate ultimately.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financially supported by the National Key Research and Development Program of China(No.2023YFD2200505)the National Natural Science Foundation of China(No.22202105)+3 种基金the Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.21KJA150003)the Innovation and Entrepreneurship Team Program of Jiangsu Province(No.JSSCTD202345)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_1163)the China Postdoctoral Science Foundation(Nos.2023M731703 and 2024T170415)
文摘The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studies focus on designing homogeneous or noble metal catalysts and conducting the reactions under basic conditions.Here,we report an efficient process for the C-C bond cleavage of lignin model compounds and selectively producing esters over different shaped CeO_(2)(i.e.,nanospheres(S),nanorods(R),nanoparticles(P),and nanocubes(C))under base-free conditions.Specifically,the yield of methyl anisate from the aerobic oxidation of l-(4-methoxyphenyl)ethanol reaches 77.6%over CeO_(2)-S in one hour(91%in 9 h),exhibiting higher performance compared to other evaluated CeO_(2)catalysts(6.4%-40.2%).Extensivecharacterizations and experimental investigations reveal that the density of weak base sites and oxygen vacancies on the CeO_(2)surface is positively correlated with the yield of methyl esters.Furthermore,the reaction pathway is investigated,which confirms that 1-(4-methoxyphenyl)ethanol first undergoes two reactions(i.e.,etherification and dehydrogenation)to produce intermediates of1-methoxy-4-(1-methoxy-ethyl)-benzene and 1-(4-methoxyphenyl)ethanone,respectively,followed by a series of functional group transformations to generate the targeted methyl anisate ultimately.
