Multifunctional Tetrahydrocannabinol Derivatives as Potential Antioxidant Neuroprotectors: In Silico Targeting of Monoamine Oxidase B and Catechol-O- Methyltransferase in Parkinson’s Disease Therapy

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder linked to dopamine depletion. Inhibiting monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT), key enzymes in dopamine degradation, can enhance dopamine availability. This study explored the inhibitory potential of tetrahydrocannabinol (THC) derivatives, known for their antioxidant and neuroprotective properties. Using the CADMA-Chem strategy (Computer-Assisted Design of Multifunctional Antioxidants, which is based on Chemical properties), 111 derivatives were designed, and 16 with favorable ADMET profiles were selected. Molecular docking revealed strong binding affinities of THC30 and THC41 to MAO-B, and THC32¯ and THC49¯ to COMT. These findings suggest that selected THC derivatives may serve as promising multifunctional candidates for Parkinson’s disease therapy, pending further experimental validation.