Molecular hybrids based on Pyrazole and 4-Thiazolidinone cores: Synthesis, characterization, and anticancer studies

Abstract

A series of hybrid compounds (11a–d) bearing pyrazole (6a–d) and 4-thiazolidinone (10) cores were synthesized and characterized. The molecular structure of the compounds was determined using elemental, FT-IR, NMR, and mass spectrophotometric techniques. The stereochemistry of the molecules was determined with the aid of 1D and 2D-NMR (COSY and NOESY) techniques. MTT-based cytotoxicity assay was performed against human hepatocellular carcinoma (HepG2) cell lines to determine the anticancer potential of the hybrid compounds. Compounds 11(a–d)which adopted 2Z, 5Z-configuration showed functionality dependent anticancer activity with 11b as the most potent (IC50 = 21.13 ± 0.12 µM) while 11d as the least (IC50 = 225.0 ± 0. 29 µM). The second most potent compound 11a was found to be IC50 = 57.13± 0.20 µM followed by the third compound 11c (IC50 = 118.78 ± 0.26 µM). The results of molecular docking study also corroborated the biological results. We found that compound 11b showed highest affinity to the DNA (–8.1 kcal/mol) followed by 11a (–8.0 kcal/mol), 11c (–7.1 kcal/mol), and 11d (–8.0 kcal/mol).