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 H-1 and C-13 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.