In Silico Virtual Screening of Philippine Phytochemicals as Potential PDE4B Inhibitors for Psoriasis Using Structure-Based Molecular Docking

Psoriasis is a chronic immune-mediated skin disorder characterized by persistent inflammation, abnormal keratinocyte proliferation, and erythematous, scaly plaques. Although available treatments can manage its symptoms, long-term use may be limited by cost, adverse effects, variable patient response, and disease recurrence. This study employed a computer-aided drug-discovery workflow to identify potential phosphodiesterase-4B (PDE4B) inhibitors from phytochemicals reported in medicinal plants available in the Philippines. A library of 1,443 phytochemicals obtained from Dr. Duke’s Phytochemical and Ethnobotanical Database and the Indian Medicinal Plants, Phytochemistry and Therapeutics database was screened against PDE4B (PDB ID: 1XLX) using structure-based molecular docking on Lipinski’s Rule of Five. Twenty-two phytochemicals were shortlisted, with predicted binding affinities ranging from −10.3 to −9.0 kcal/mol, compared with −7.6 to −7.3 kcal/mol for the reference psoriasis drugs. Aurochrome obtained the most favorable initial docking score of −10.3 kcal/mol and a predicted dissociation constant of 28.16 nM. The four leading compounds Aurochrome, Friedelin, Kakkanin, and Taraxerone, were subjected to 100-ps molecular dynamics simulations. Friedelin was selected as the leading computational candidate because its third-ranked pose exhibited preliminary RMSD stability, a binding affinity of −9.1 kcal/mol, a predicted dissociation constant of 213.44 nM, 17 van der Waals interactions, and compliance with the study’s Lipinski criterion with one violation. Friedelin is reported in locally available plants, including kataka-taka, tawa-tawa, atis, and maize. These findings identify Friedelin as a preliminary computational hit rather than a confirmed psoriasis treatment. Further ADMET profiling, PDE-isoform selectivity testing, longer molecular dynamics simulations, enzyme-inhibition assays, toxicity assessment, and in vivo validation are required.