Comprehensive in silico analysis of 5,7-dimethoxycoumarin (citropten): pharmacokinetic, toxicological, and multi-target docking insights for potential neuropharmacological applications

Abstract Background: 5,7-Dimethoxycoumarin (citropten) is a naturally occurring coumarin known for its antioxidant and neuroprotective effects. However, its drug-likeness, pharmacokinetic characteristics, toxicity, and interactions with neuropharmacological targets have not been comprehensively investigated. This study aimed to conduct an integrated in silico assessment of citropten to evaluate its potential as a therapeutic candidate for central nervous system (CNS) disorders. Materials and Methods: Pharmacokinetic and drug-likeness properties were analyzed using SwissADME, pkCSM, PreADMET, and ADMETlab 2.0. Toxicity predictions were performed with ProTox-3.0, pkCSM, and ADMETlab 2.0. Molecular docking studies were carried out using Schrödinger GLIDE against seven CNS-relevant targets: monoamine oxidase A (MAO-A), monoamine oxidase B, acetylcholinesterase (AChE), 5-hydroxytryptamine receptors [5-hydroxytryptamine (serotonin) receptor 1A and 5-hydroxytryptamine type 3 receptor (5-HT3)], α7 nicotinic acetylcholine receptor, and dopamine D2 receptor. Results: Citropten complied with all major drug-likeness criteria and demonstrated high gastrointestinal absorption, efficient blood–brain barrier permeability, and moderate plasma protein binding. It selectively inhibited cytochrome P450 family 1 subfamily A member 2 with minimal potential for drug–drug interactions. Toxicity predictions indicated low acute toxicity (Class V), with no major organ toxicity alerts, except for minor receptor-level alerts such as Ames mutagenicity and eye irritation. Docking analyses revealed strong binding affinities toward MAO-A, AChE, and 5-HT3 receptors, supported by hydrogen bonding and π–π stacking interactions, suggesting possible multi-target neuropharmacological activity. Conclusion: This study provides the first comprehensive in silico characterization of citropten, highlighting its favorable pharmacokinetic, safety, and multi-target binding profiles. These results indicate that citropten may interact with molecular targets relevant to neurodegenerative and neuropsychiatric disorders; however, these computational findings are only predictive and require thorough experimental and preclinical validation before any therapeutic role can be inferred.