Curcumin based pyrazole-thiazole hybrids as antiproliferative agents: Synthesis, pharmacokinetic, photophysical properties, and docking studies

Abstract

A series of new curcumin pyrazole-thiazole hybrids (C1-C8) were synthesized and characterized by fundamental spectral analysis. The synthesized compounds were tested for antiproliferative activity against the colorectal cancer cell line (COLO-205), breast cancer cell line (MCF-7), liver cancer cell line (HepG-2), lung cancer cell line (A549), and cervical cancer cell line (HeLa) using cisplatin as a positive control. The compounds C7 (IC50 values of 8.57 ± 1.09 µM for COLO-205, 9.22 ± 0.73 µM for MCF-7, 16.95 ± 1.16 µM for HepG-2, 8.48 ± 1.36 µM for A549, and 7.22 ± 1.08 µM for HeLa), C2, and C5 displayed the most potent antiproliferative activity against the growth of all tested cell lines. For the three compounds (C2, C5, and C7), which were shown to have high in vitro anti-cancer activity, we have carried out a kinase inhibitory assay against the EGFR and HER2, where the compound C7 has exhibited double inhibitory potency towards the EGFR when compared to reference erlotinib. Furthermore, in silico molecular docking studies on EGFR (PDB ID: 4HJ0) and HER2 (PDB ID: 3P0Z) proteins revealed that the potent ligands exhibited higher affinity with an active pocket of receptors showing strong hydrogen bond interactions. The compounds C5 and C2 showed potent antioxidant activity. In addition, the drug-likeness of the hybrids was assessed by predicting their physicochemical, pharmacokinetic (ADME), toxicity profiles, and photophysical properties.