Multi-Target In Silico Evaluation of Bioactive Phytocompounds from Irvingia gabonensis Seeds Against Oncogenic Proteins: A Computational Drug Discovery Perspective

Cancer remains a leading cause of mortality in sub-Saharan Africa, with limited access to targeted therapies driving demand for affordable, novel lead compounds. Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill., known as ogbono or African bush mango, is a nutritional staple across West and Central Africa whose seed harbours bioactive phytochemicals. Molecular docking studies were conducted using AutoDock Vina (version 1.2.0) against three oncogenic targets: Bcl-2 (PDB: 6O0K), phosphoinositide 3-kinase gamma (PI3K-gamma; PDB: 1E8X), and the nuclear factor kappa-B p65 subunit (NF-kB p65; PDB: 2RAM). Five phytocompounds, namely ellagic acid, quercetin, kaempferol, lupeol, and beta-sitosterol, were evaluated alongside three reference drugs: venetoclax, idelalisib, and BAY 11-7082. Pharmacokinetic profiling was assessed through Lipinski, Veber, and Ghose drug-likeness filters, and ADMET properties were predicted using computational descriptors. Quercetin exhibited the highest binding affinity among phytocompounds, recording -9.1 kcal/mol against PI3K-gamma and -8.9 kcal/mol against Bcl-2, approaching reference idelalisib (-9.8 kcal/mol). Kaempferol and ellagic acid demonstrated consistent multi-target engagement across all three proteins. Four of five phytocompounds satisfied Lipinski criteria with zero or one violation. ADMET analysis revealed favourable safety profiles relative to reference drugs, with no predicted hERG inhibition or hepatotoxicity across phytocompounds. The phytocompound matrix of I. gabonensis seeds constitutes a computationally validated multi-target oncological scaffold. Quercetin and kaempferol emerge as priority leads for further in vitro validation. This study provides a reproducible computational framework and advances the case for repositioning an African food crop as a natural product lead in cancer drug discovery