Molecular docking and anticancer evaluation of some newly synthesized 4-aryl-2-(2-oxopropoxy)-6-(cyclohexyl)nicotinonitrile and their furo[2,3-b]pyridine derivatives

1-(3-Amino-6-cyclohexylfuro[2,3-b]pyridin-2-yl)ethan-1-one derivatives 3a-f carrying aryl substituents at position 4 were synthesized in two steps. The 6-cyclohexyl-2-oxo-1,2-dihydropyridine-3-carbonitriles 1a-f, as key compounds, were converted to the corresponding 6-cyclohexyl-2-(2-oxopropoxy)nicotinonitriles 2a-f, followed by the Thorpe-Ziegler ring cyclization to compounds 3a-f. Moreover, the in vitro cytotoxicity evaluation of the new compounds has been assessed against four cancer cell lines: A549 (lung carcinoma), HCT116 (colon), PACA2 (Pancreatic cancer) and MCF7 (Human Caucasian breast adenocarcinoma), utilizing doxorubicin as a reference drug. The results revealed that the nicotinonitrile derivatives 2a-f were the most potent and selective for the lung carcinoma (A549) inhibition, in particular compounds 2d and 2f, while the furo[2,3-b]pyridine derivatives 3b,c,e,f represented selective promising inhibition activity against the breast cancer (MCF7) cell line. Finally, a good correlation was obtained between the observed cytotoxicity evaluation of compounds 2d and 2f against A549 (lung carcinoma), from one side, and the molecular descriptors from another side.