Design, synthesis and anticancer activity of new 3-cyano-2 (1H) -pyridone and 3-cyanopyridine-2-(1H)-thione Derivatives

The main objective of the present research study is to synthesize some novel chalcone, cyanoacetohydrazone, enaminone, 3-cyano-2(1H)-pyridone and 3-cyanopyridine-2-(1H)-thione derivatives and evaluate them for their anticancer effect. The novel chalcones 2a-c were achieved by Claisen-Schmidt condensation of appropriate benzaldehydes with ethanone derivative 1. Treatment of cyanoacetic acid hydrazide with ethanone derivative 1 yielded the correspondinghydrazone derivative 3. Condensation of ethanone derivative 1 with DMF-DMA afforded (E)-3-(dimethylamino)-1-(4-morpholinophenyl) prop-2-en-1-one 4. Heterocyclization of chalcones 2a-c with cyanothioacetamide yielded 2-thioxo-1,2-dihydropyridine-3-carbonitriles 7ac. In a similar manner, cyclocondensation of chalcones 2a, b with cyanoacetamide afforded the corresponding 2-oxo-1,2-dihydropyridine-3-carbonitriles 8a, b. The Reaction of compound 2a with ethyl cyanoacetate furnished 2-oxo-1,2-dihydropyridine-3-carboxylate 12. The 2-oxo-4-phenyl-1,2- dihydro-pyridine-3,5-dicarbonitriles 14a, b were obtained by cyclization of cyanoacetohydrazone 3 with cinnamonitriles. The structures of the synthesized compounds were confirmed by elemental analysis, mass spectrometry, IR and H-1-NMR spectroscopy. The anticancer activity of the newly synthesized compounds was screened in vitro against Human lung carcinoma (A 549) cell line indicating that compounds 7b and 8a possess the most potent inhibitory effect against the human lung carcinoma cell line (A549).