Biological Activities, DFT Calculations, and Molecular Docking Simulation of Thymol‐Based Compounds

Abstract A set of thymol‐based derivatives ( 3 a – d ) was synthesized and characterized. Quantum chemical calculations were performed to explain the nature of the transitions in the absorption spectra. These new compounds were tested as anticancer agents on human liver (HepG2), lung (A549), and colon (DLD‐1) cancer cell lines using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide method showing in some cases higher antiproliferative properties than the reference drug cisplatin. All synthesized compounds were also screened for their antimicrobial activity against a representative panel of Gram‐positive and Gram‐negative bacteria plus a pathogenic yeast species ( Candida albicans ATCC90028) using agar disc diffusion and broth microdilution assays. Furthermore, we determined the antioxidant activity of these compounds by the DPPH free radical scavenging test. According to the minimum bactericidal concentration, minimum fungicidal concentration, and IC 50 values, compound 3 c showed the highest antimicrobial activity, compound 3 d exhibited the highest antioxidant activity, while compounds 3 b and 3 c displayed higher cytotoxic activity than cisplatin against HepG2 and DLD‐1 cell lines albeit no selectivity towards healthy cells (HEK‐293T). Furthermore, docking simulations of the compounds towards two potential molecular targets, namely caspase‐3 protein (PDB ID: 3KJF) and Escherichia coli glucosamine‐6‐phosphate synthase (PDB ID: 2VF5), were performed in order to validate the anticancer and antimicrobial activities, respectively.