Thymol and carvacrol derivatives as anticancer agents; synthesis, in vitro activity, and computational analysis of biological targets

Abstract

Various thymol and carvacrol derivatives have been synthesized to test the anticancer activity potential. Computational methods including network pharmacology and molecular docking approaches were utilized to identify and assess the potential biological targets relating to cancer. Amongst the synthesized derivatives the ethoxy-cyclohexyl analogues were consistently the most active against a panel of 10 different cancer cell lines covering a variety of origins. Biological target predictions revealed the AKT1 protein to be a core and central target of the most active compounds. Molecular docking identified a binding pocket within this protein in which the most active compounds bind. The incorporation of computational analysis methods and conventional structure–activity approaches identified analogues of thymol and carvacrol with the highest anticancer potential, and analyzed their possible biological targets in a comprehensive manner.