1Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
2Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Cancer is a leading cause of death worldwide. Despite the availability of several chemotherapeutic drugs, there is still a great need for more efficient agents for a better management of cancer. In this contribution, a series of 11 DHPs (4a, 4b & 7a-i) were synthesized and evaluated for their cytotoxic effect against MCF-7, LS180, and MOLT-4 cancer cell lines using MTT assay. Synthesized 2,6-dimethyl-3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridines exhibited different potencies ranging from weak to good cytotoxic activities, while no activity could be recorded for 1,4-bis(2,6-dimethyl-3,5-dimethoxylcarbonyl-1,4-dihydropyridine-4-yl) benzene compounds (4a & 4b). Tested DHP derivatives were more potent against MOLT-4 cells, when compared to LS180 and MCF-7 cells. Compounds 7d (IC50=28.5±3.5 µM), 7a (IC50=29.7±4.7 µM) and 7a (IC50=17.4±2.0 µM) were the most potent derivatives against MCF-7, LS180 and MOLT-4 cells, respectively. It appeared that the introduction of N-thiazolyl carbamoyl group at the C3 and C5 positions of DHP ring enhanced the cytotoxic potential of these derivatives (compounds 7a-e). The findings of this study suggest that some of the thiazole substituted 1,4-DHPs may be candidates for further modifications towards the discovery of potent antitumoral agents.