Design, synthesis and biological evaluation of novel chalcone-derived thioxopyridine and pyrazolopyridine compounds...

The present work deals with the synthesis of some new chalcone, 2- thioxopyridine,2-methylthiopyridine, 2-hydrazinopyridine and 3-amino-1H-pyrazolo[3,4-b]pyridine derivatives containing biologically active substituents. The starting material of the present study was synthesis of the 2-cyanoethanethioamide from malononitrile using a modified Brunskill procedure, followed by the synthesis of the 1,3-diarylprop-2-en-1-one (chalcone) from a ketone and an aldehyde. 2-Thioxopyridines were obtained through Michael addition of α,β-unsaturated ketones with 2-cyanothioacetamide to afford the non-isolable intermediates 8 & 9 followed by cyclization and subsequent dehydration and dehydrogenation of the cyclized product to give compound 4-(furan-2-yl)-6-(4- methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile which was reacted with methyl iodide in methanolic sodium methoxide to afford the corresponding 4-(furan-2-yl)-6-(4-methoxyphenyl)-2-(methylthio) pyridine-3-carbonitrile, which was reacted with hydrazine hydrate to give the corresponding 2-hydrazinopyridines, which cyclized to afford the corresponding 3-aminopyrazolo[3,4-b]pyridine derivatives and were characterized by FT-IR, ¹H-NMR, ¹³C-NMR and MS spectral studies. All the newly synthesized compounds were evaluated for their in vitro antibacterial activity against S. aureus as example of Gram-positive bacteria and E. coli as example of Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential effect against C. albicans. The zone of inhibition was measured using the well diffusion assay, and the results indicated that compounds 3, 5, 10 and 13 showed potential antibacterial and antifungal effects.