Synthesis, characterization and cytotoxicity properties of new dichlorothiophene based nicotinonitrile derivatives

New pyridine-carbonitrile derivatives (1?16) were synthesized and characterized. Some of these derivatives, (7?9) and (15?16), were formed as minor products by decyanation of the corresponding pyridine-carbonitriles main product. By using various spectral techniques, IR, 1H and 13C NMR, 2D NMR (COSY, HSQC, and HMBC) experiments, and electrospray ionization high-resolution mass spectrometry (ESI-HRMS), structure have been proposed for all derivatives and, for derivative 10, additionally confirmed by single crystal structural analysis. The molecular structure of 10 is composed of a central 2-methoxypyridine-3-carbonitrile ring with two substituents in positions 4 (furan-2-yl) and 6 (5-chlorothiophen-2-yl). Crystal structure is stabilized by C?H???O/N hydrogen bonding, ????? stacking, and by C?H???? interactions. The cytotoxicity of all derivatives was assessed against four cell lines, namely, normal skin fibroblast, K562 (leukemia), MCF7 (breast cancer) and HCT116 (colon cancer). Cytotoxicity analysis results revealed that compound 11 had moderate cytotoxicity toward the leukemia (K562) and breast cancer (MCF7) cell lines. An interesting result was obtained for compound 1 which was toxic toward normal skin fibroblasts but highly toxic toward the MCF7 cell lines, with a half maximal inhibitory concentration [IC50] of 1.7 ? 0.3 ?M and an IC50 selectivity ratio of 19.3. Compound 1 inhibited skin fibroblasts by 8% at a concentration of 3 ?M. The two compounds are considered potential candidates for anticancer drugs.