3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 603-607)
АУТОР(И) / AUTHOR(S): Kristina D. Milisavljević, Svetlana R. Jeremić, Jovana D. Matić, Žiko B. Milanović
Download Full Pdf 
DOI: 10.46793/ICCBIKG25.603M
САЖЕТАК / 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.
КЉУЧНЕ РЕЧИ / KEYWORDS:
Parkinson’s Disease, tetrahydrocannabinol (THC), monoamine oxidase type B (MAO-B), catechol-O-methyltransferase (COMT), molecular docking
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This research is funded by the Ministry of Education and the Ministry of Science, Technological Development and Innovation, Republic of Serbia, Grants: No. 451-03- 136/2025-03/200378 and 451-03-65/2024-03/200252.
ЛИТЕРАТУРА / REFERENCES:
- T. F. Sampaio, E.U.D. Dos Santos, G.D.C. de Lima, R.S.G. Dos Anjos, R.C. da Silva, A.G.C. Asano, P.R.E. de Souza, MAO-B and COMT genetic variations associated with levodopa treatment response in patients with Parkinson’s disease, The Journal of Clinical Pharmacology, 58 (2018) 920–926.
- M. Regensburger, C.W. Ip, Z. Kohl, C. Schrader, P.P. Urban, J. Kassubek, W.H. Jost, Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: Practical considerations, Journal of Neural Transmission, 130 (2023) 847–861.
- E. B. Malabadi, K.P. Kolkar, R.K. Chalannavar, Δ9-Tetrahydrocannabinol (THC): The major psychoactive component is of botanical origin, Int. J. Innov. Sci. Res. Rev., 5 (2023) 4177–4184.
- E. G. Guzman-Lopez, M. Reina, A. Perez-Gonzalez, M. Francisco-Marquez, L.F. Hernandez- Ayala, R. Castañeda-Arriaga, A. Galano, CADMA-Chem: a computational protocol based on chemical properties aimed to design multifunctional antioxidants, International Journal of Molecular Sciences, 23 (2022) 13246.
- L. Fu, S. Shi, J. Yi, N. Wang, Y. He, Z. Wu, D. Cao, ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support, Nucleic Acids Research, (2024) gkae236.
- C. Binda, J. Wang, L. Pisani, C. Caccia, A. Carotti, P. Salvati, A. Mattevi, Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs, Journal of Medicinal Chemistry, 50 (2007) 5848–5852.
- A. Ehler, J. Benz, D. Schlatter, M.G. Rudolph, Mapping the conformational space accessible to catechol-O-methyltransferase, Acta Crystallographica Section D: Biological Crystallography, 70 (2014) 2163–2174
- G. M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30 (2009) 2785–2791.