Design, Synthesis, and Anticancer Activity Evaluation of Hybrids of Azoles and Barbituric Acids

Document Type: Research article

Authors

Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.

10.22037/ijpr.2020.113547.14363

Abstract

 In order to find new drugs with potent antiproliferative effect, a series of novel barbituric acid derivatives containing azoles at the C-5 position were designed, synthesized, and evaluated for antiproliferative activity against three human cancer cell lines (BEL-7402, MCF-7, and HCT-116) using MTT assay. Several of the synthesized compounds exhibited potent antiproliferative effects. The most promising compound was 5-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl) methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (3s), which showed considerably high antiproliferative activity in the BEL-7402 cell line, with a half-maximal  inhibitory concentration of 4.02 µM and 20.45-fold higher selectivity for BEL-7402 cells than for normal L02 cells. The apoptosis experiment showed that compound 3s induced apoptosis and cell necrosis in a concentration-dependent manner and exert its anti-proliferative activity. Therefore, compound 3s exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil.

Graphical Abstract

Design, Synthesis, and Anticancer Activity Evaluation of Hybrids of Azoles and Barbituric Acids

Keywords