Abstract
A series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a-m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all the synthesized compounds were accomplished by spectral data, IR, H-1 NMR, C-13 NMR, MS, and elemental analyses. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. The cancer cells were treated with the synthesized compounds at differentiable dosages, and cell viability was determined. Compounds 4e, 4f, and 4m exhibited excellent antitumor activity versus all cancer cell lines with IC50 values ranging from 0.2 to 1.7 mu M. The cell cycle arrest behavior of compounds 4e, 4f, and 4m was investigated. The results illustrated that the potent cytotoxic compounds 4e, 4f, and 4m induce cell cycle arrest at the G2/M phases and trigger apoptosis in the different tested cancer cells. Finally, the structure activity relationship (SAR) survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of certain substituents at certain positions.