IN SILICO APPROACHES ON PHENYLALANINE HYDROXYLASE INHIBITOR-RELATED COMPOUNDS USED IN PARKINSON’S DISEASE TREATMENT

Abstract

Objective: In Parkinson’s disease, Levodopa with Carbidopa addresses dopamine deficiency. Phenylalanine hydroxylase catalyzes phenylalanine to tyrosine conversion crucial for dopamine synthesis. Inhibiting phenylalanine hydroxylase may enhance Carbidopa's effects, preventing peripheral dopamine synthesis. The study used virtual scanning, molecular docking, and dynamics simulation to explore phenylalanine hydroxylase interactions with Carbidopa and similar ligands. ADME/T assessments and drug similarity tests were conducted to evaluate therapeutic potential in biological systems. Material and Method: A molecular docking study was performed on the structures obtained from the PubChem database and human PAH (PDB ID: 6PAH) using Autodock Vina within Chimera 1.16. Furthermore, the ligands underwent ADME/T assays, which are crucial aspects in drug development. Result and Discussion: The study suggests that 2-(2-Aminohydrazinyl)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid shows promise as a phenylalanine hydroxylase inhibitor for Parkinson's disease treatment, but further research is needed to assess its safety, efficacy, and specificity, particularly in extracerebral regions, while also exploring its potential to improve the effectiveness of Levadopa/Carbidopa combination therapy.