Antioxidant, Antimicrobial and Enzyme Inhibitory Activities of Carvone, Thymol and Camphor: An In Vitro Study Integrated With Molecular Docking, Molecular Dynamics Simulations and <scp>ADMET</scp> Predictions

ABSTRACT This study aimed to investigate the antioxidant, antidiabetic, anticholinesterase, dermatoprotective effects, and antimicrobial properties of carvone, thymol and camphor. The antioxidant activity of these monoterpenes was performed by six methods: DPPH, FRAP, CUPRAC, MAC, PBD, and ABTS. The antidiabetic potential was assessed through the inhibition of both α ‐amylase and α ‐glucosidase; the inhibition of tyrosinase was assessed to study the dermatoprotective properties, while the antimicrobial efficiency was assessed based on both the agar well diffusion and the microtitration methods. Additionally, in silico investigations combining both molecular docking and dynamics (MD) simulations were conducted to explain the main findings. Thymol demonstrates the highest antioxidant capacity in four of the six assays (FRAP, CUPRAC, ABTS and DPPH). Carvone presents a mechanistically distinct antioxidant profile from thymol, excelling in metal chelation (MAC) and total reducing capacity (PBD), which represents the most scientifically noteworthy finding among the six assays. The three compounds significantly inhibited tyrosinase, with carvone displaying the highest effect (32.518 ± 4.419 mg KAE/g). A notable efficacy against BChE was exhibited; however, no compound inhibited the AChE enzyme. Moreover, modest inhibition of α ‐amylase was recorded while thymol and camphor exhibited a modest effect on α ‐glucosidase, with comparable values (1.432 ± 0.023 and 1.431 ± 0.025 mM ACAE/g, respectively). In addition, carvone has been shown to be highly effective with a bactericidal effect against P. aeruginosa , L. monocytogenes , E. coli and S. aureus , whereas thymol and camphor did not show any effect on the four bacterial strains, whereas no anticandidal effect was reported. Molecular docking demonstrated that carvone, thymol and camphor occupied the active site of the examined enzymes via different interactions, while MD simulation helped to corroborate the in vitro findings. Furthermore, ADMET prediction indicated that carvone, thymol and camphor had favourable ADMET profiles. In summary, carvone, thymol, and camphor may be promising as tyrosinase and α ‐glucosidase inhibitors and/or as lead compounds for developing new semisynthetic drugs for treating diabetes and pigmentation disorders.