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 development of efficient systems for the catalytic oxidation of 2-nitro-4-methylsulfonyltoluene(NMST)to 2-nitro-4-methylsulfonyl benzoic acid(NMSBA)with atmospheric air or molecular oxygen in alkaline medium prese...The development of efficient systems for the catalytic oxidation of 2-nitro-4-methylsulfonyltoluene(NMST)to 2-nitro-4-methylsulfonyl benzoic acid(NMSBA)with atmospheric air or molecular oxygen in alkaline medium presents a significant challenge for the chemical industry.Here,we report the synthesis of FeOOH/Fe_(3)O_(4)/metal-organic framework(MOF)polygonal mesopores microflower templated from a MIL-88B(Fe)at room temperature,which exposes polygonal mesopores with atomistic edge steps and lattice defects.The obtained FeOOH/Fe_(3)O_(4)/MOF catalyst was adsorbed onto glass beads and then introduced into the microchannel reactor.In the alkaline environment,oxygen was used as oxidant to catalyze the oxidation of NMST to NMSBA,showing impressive performance.This sustainable system utilizes oxygen as a clean oxidant in an inexpensive and environmentally friendly NaOH/methanol mixture.The position and type of substituent critically affect the products.Additionally,this sustainable protocol enabled gram-scale preparation of carboxylic acid and benzyl alcohol derivatives with high chemoselectivities.Finally,the reactions can be conducted in a pressure reactor,which can conserve oxygen and prevent solvent loss.Moreover,compared with the traditional batch reactor,the self-built microchannel reactor can accelerate the reaction rate,shorten the reaction time,and enhance the selectivity of catalytic oxidation reactions.This approach contributes to environmental protection and holds potential for industrial applications.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supported by the National Natural Science Foundation of China(22078251)Hubei Province Key Research and Development Program(2023DJC167)the research project of Hubei Provincial Department of Education(D20191504).
文摘The development of efficient systems for the catalytic oxidation of 2-nitro-4-methylsulfonyltoluene(NMST)to 2-nitro-4-methylsulfonyl benzoic acid(NMSBA)with atmospheric air or molecular oxygen in alkaline medium presents a significant challenge for the chemical industry.Here,we report the synthesis of FeOOH/Fe_(3)O_(4)/metal-organic framework(MOF)polygonal mesopores microflower templated from a MIL-88B(Fe)at room temperature,which exposes polygonal mesopores with atomistic edge steps and lattice defects.The obtained FeOOH/Fe_(3)O_(4)/MOF catalyst was adsorbed onto glass beads and then introduced into the microchannel reactor.In the alkaline environment,oxygen was used as oxidant to catalyze the oxidation of NMST to NMSBA,showing impressive performance.This sustainable system utilizes oxygen as a clean oxidant in an inexpensive and environmentally friendly NaOH/methanol mixture.The position and type of substituent critically affect the products.Additionally,this sustainable protocol enabled gram-scale preparation of carboxylic acid and benzyl alcohol derivatives with high chemoselectivities.Finally,the reactions can be conducted in a pressure reactor,which can conserve oxygen and prevent solvent loss.Moreover,compared with the traditional batch reactor,the self-built microchannel reactor can accelerate the reaction rate,shorten the reaction time,and enhance the selectivity of catalytic oxidation reactions.This approach contributes to environmental protection and holds potential for industrial applications.
