Molecular modeling and cytotoxic activity of new thiadiazole-pyrazole hybridized with thiazole

Abstract

The thiadiazole-pyrazole hybrid 3 was synthesized by treating 2-cyano-3,3-bis(methylthio)-N-(5-phenyl-1,3,4-thiadiazol-2-yl)acrylamide (2) with hydrazine hydrate, and employed in the production of four thiadiazole-pyrazole compounds 5 and 6a-c that hybridized with the thiazolidin-4-one ring system. The frontier molecular orbitals of the synthesized hybrids were investigated using DFT/B3LYP methodology to study their configuration and energetic properties. The results revealed that they had a small energy gap (ΔEH-L), 1.93–3.08 eV, and may be sorted as 6b < 6a < 6c < 3 < 4 < 5. The synthesized thiadiazole-pyrazole hybridized with thiazole derivatives were screened toward several cell lines; HepG2, A549, MCF-7, and HCT-116. The thiadiazole-pyrazole-thiazole hybrids 6a-c displayed significant antitumor activities, with an IC50 (29.30±0.16 to 36.03±0.65 μM) toward HepG2, IC50 (28.56±0.36 to 37.16±0.52 μM) toward the A549 cell line. Moreover, thiadiazole-pyrazole hybridized with thiazole derivatives were subjected to the crystal structure of caspase-3 1RHJ to check the binding appropriateness scores of bio-active skeletons besides their definite effects on the caspase-3 enzyme.