Cannabidiol-Based Thiosemicarbazones: A Preliminary Study Evaluating Their Anti-Tyrosinase Properties

Cannabidiol (CBD), a non-psychoactive cannabinoid, has attracted significant research interest due to its antioxidant, anti-inflammatory, and neuroprotective properties. As a versatile scaffold in drug discovery, CBD has been widely explored for developing novel therapeutics. In this study, we synthesized and evaluated the anti-tyrosinase activity of CBD-based thiosemicarbazones. Structure-activity relationship (SAR) analyses were conducted to assess the impact of various functional groups on tyrosinase inhibition, including an evaluation of inhibitory kinetics for selected compounds. The synthesized derivatives demonstrated potent tyrosinase inhibition, with activity comparable to kojic acid, a standard tyrosinase inhibitor. Given the crucial role of tyrosinase in melanin biosynthesis, these findings suggest that CBD-based thiosemicarbazones could serve as promising candidates for managing tyrosinase-related disorders, including hyperpigmentation and melanogenesis-related conditions. Moreover, the presence of thiosemicarbazone moieties may contribute to the observed inhibitory effects, potentially through metal chelation at the enzyme's active site. This study provides valuable insights into the design of CBD-derived inhibitors targeting tyrosinase. Further optimization and in-depth biological evaluation are warranted to explore their full therapeutic potential.