Synthesis and characterization of novel thiazole derivatives as potential anticancer agents: Molecular docking and DFT studies

Abstract

New thiazole derivatives (2a-l) were synthesized via the reaction of 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid with substituted phenyl amines. The anticancer activity of the synthesized thiazole derivatives was examined against MCF-7 (human breast), MDA-MB-231 (mammary carcinomas), HeLa (Cervical cancer), HT-29, HCT 116 (Colon cancer), and normal chang liver cancer cell lines, whereas cisplatin was employed as a positive control. The anticancer mechanisms were studied via apoptosis assessments, as well as molecular docking. The molecular docking study of potent compounds was carried out against the human epidermal growth factor receptor (HER2, PDB ID: 3RCD) as a possible target for anticancer activity using Auto Dock vina. ADMET results indicated that tested compounds have significant results within the close agreement of Lipinski’s rule of five. In addition, computational work employing density functional theory (DFT) was also carried out at the B3LYP/6-31G (d,p) level to investigate the electronic properties of the potent compounds. The frontier molecular orbital energy and atomic net charges were discussed.