Synthesis, modeling, and biological studies of new thiazole-pyrazole analogues as anticancer agents

Abstract

A series of various substituted thiazole-pyrazole hybrids 5, 7, 8, and 9 were synthesized, and their chemical structures were confirmed by spectral data (infrared, 1H & 13C NMR and Mass). The frontier molecular orbital structural and energetic properties of the targeting thiazole-pyrazole hybrids were explored using the DFT/B3LYP methodology. The data indicated that they had a low energy gap (ΔEH-L), 1.51–2.42 eV, and may be sorted as 6 9 > 7 > 6. Meanwhile, most of the synthesized analogues displayed a significant reduction for the activity of the CAIX inhibitor, with IC50 = 0.071 ± 0.015 to 0.902 ± 0.043 µM. Likewise, they revealed an IC50 = 0.119 ± 0.043 to 0.906 ± 0.04 µM for CAXII inhibitor. Moreover, the newly synthesized thiazole-pyrazole analogues were exposed to the theoretical molecular docking study with PDB:1RHJ as the crystal structure of caspase-3 to examine their antiapoptotic effect as well as their certain properties on the caspase-3 enzyme.

Keywords

• Thiosemicarbazone
• 4-chlorophenacyl bromide
• Thiazole-pyrazole hybrids
• DFT/B3LYP
• Cytotoxicity
• Carbonic anhydrases