Design and In Silico Study of 3,5-Dinitrocatechol and Its Derivatives for Antiparkinsonian Activity

Parkinson's disease (PD) is a neurodegenerative disorder marked by dopamine deficiency in the brain. Catechol-O-methyltransferase (COMT) is an enzyme responsible for the degradation of dopamine, and its inhibition can prolong dopamine activity. The current study focuses on designing and evaluating derivatives of 3,5-dinitrocatechol (DNC) through in silico methods for potential COMT inhibition. The crystal structure of the COMT enzyme (PDB: 4XUC) was used as the receptor for molecular docking studies. Entacapone, a standard COMT inhibitor, was used as a reference drug. Six derivatives of DNC were designed and analyzed using PyRx for docking, SwissADME for pharmacokinetic analysis, and ProTox-II for toxicity prediction. Among the derivatives, D6 showed the highest binding affinity (-6.6 kcal/mol) compared to Entacapone (-5.5 kcal/mol), with good ADME properties and minimal toxicity. The results indicate D6 as a promising COMT inhibitor candidate for Parkinson’s therapy.