熊果酸—二硫代氨基甲酸酯缀合物的合成及其广谱抗肿瘤活性评价OA

Objective The purpose of this paper is to establish a mild and readily accessible synthetic method to prepare ursolic acid(UA)-dithiocarbamate derivatives,and evaluation of their antitumor activities.Methods By virtue of the pharmacophore hybrid strategy,we report a two-step protocol to obtain a series of structurally novel UA-dithiocarbamate conjugates in mild conditions with high yields.All of the compounds were characterized by 1H-NMR,13C-NMR and high-resolution mass spectrometry.Moreover,their antitumor activities were preliminarily evaluated.Results Twenty novel UA-dithiocarbamate conjugates(3a-3t)were synthesized.After preliminary bioactivity evaluation,most of the new compounds showed certain growth inhibition effects on six cancer cell lines,including Panc1,A549,Hep3B,Huh-7,HT-29 and Hela.The results of drug function experiments showed that compound 3d could inhibit the invasion and migration of Huh-7 cells,and induce the apoptosis of Huh-7 cells in a dose-dependent manner.Conclusion We have synthesized a series of UA-dithiocarbamate derivatives in a two-step protocol at room temperature,offering a readily acces-sible synthetic route to obtain novel UA derivatives in high yields.The compound 3d containing hydroxyl substituents exhibited the best antitumor activity.