Synthesis, characterization, and antioxidant activity of thymol-based paracetamol analogues

Thymol (2-isopropyl-5-methylphenol) is an important monoterpene phenol occurring in the essential oils isolated from Thymus vulgaris , Thymus zygis , Thymus hyemalis , etc. Thymol and its derivatives show various activities such as antioxidant, antiinflammatory, antibacterial, and antifungal effects. In the present study, a set of new benzamide derivatives ( 4a – e ), which are structurally similar to paracetamol, were synthesized from thymol using a green synthetic approach and characterized by Fourier-transform infrared (FT-IR) and 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopies, liquid chromatography–mass spectrometry (LC–MS), and X-ray single-crystallographic analysis for derivative 4c . These derivatives were subjected to antioxidant testing by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and antibacterial testing against five microorganisms. Molecular docking studies of all the compounds indicated that they are good inhibitors of heme oxygenase-1. These results extend the development of thymol-based benzamide scaffolds as promising antioxidant agents.