Microwave-assisted synthesis of new fluorinated coumarin–pyrimidine hybrids as potent anticancer agents, their DNA cleavage and X-ray crystal studies

Abstract

An efficient and rapid synthesis of 3-(2-(4-fluorobenzyl)-6-(substituted phenyl) pyrimidin-4-yl)-2H-chromen-2-one derivatives (1a–1l) under microwave-irradiation has been described in high yields. All the newly synthesized compounds (1a–1l) were characterized by elemental and spectroscopic analysis. In addition, the structure of compound (1a) and (1b) has been elucidated by the single crystal X-ray diffraction technique. The synthesized compounds (1a–1l) were evaluated for their anticancer activity against two human cancer cell lines viz., A-549 (human lung carcinoma) and MDA-MB-231 (human adenocarcinoma mammary gland). The results revealed that several synthesized compounds exhibit significant cytotoxicity against the two tested cancer cell lines with IC₅₀ < 10 μM. Among these, compound (1j) exhibited potent activity against the A-549 cell line, which is comparable with standard drug Cisplatin, whereas compound (1b) was found extremely active against the MDA-MB-231 cell line and proved to be more potent than standard drug Cisplatin. DNA cleavage study by the gel electrophoresis method revealed that compounds (1b), (1e), (1g) and (1j) inhibit the growth of the pathogenic organism by cleaving the genome as no traces of DNA were found.