Anti-Prostatic Carcinoma Activity of Entandrophragma angolense and Methyl Angolensate: In Vitro and In Silico Analyses

Objectives/Background: Prostate cancer is the second most diagnosed malignancy among men globally. In Ghana, the age-standardized mortality rate aligns with global trends, reflecting low survival rates largely due to limited access to cancer care and the high cost of therapies. This has increased reliance on traditional medicine, much of which remains scientifically unverified. This study aimed to evaluate the cytotoxic and pharmacological potential of Entandrophragma angolense stem bark extract and its bioactive metabolite, methyl angolensate, in prostate cancer models. Methods: Cytotoxic activity was evaluated using the Alamar Blue assay across five prostate cancer cell lines (LNCaP, PC-3, DU-145, 22Rv1, VCaP) and one normal prostate epithelial line (RWPE-1). Molecular docking assessed the interaction of methyl angolensate with the androgen receptor (AR), using metribolone as a reference. Molecular dynamics (MD) simulations totaling 100 ns were performed to evaluate the stability of ligand–AR complexes. Pharmacokinetic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were assessed in silico using ADMETLab 2.0. Results: The extract and methyl angolensate reduced viability by over 40% in AR-positive cell lines (LNCaP, VCaP, 22Rv1) while showing <10% effect on RWPE-1 cells. Methyl angolensate demonstrated a strong binding affinity to AR (ΔG = −16.5 kcal/mol), exceeding that of metribolone (ΔG = −7.6 kcal/mol). MD simulations confirmed stable AR–ligand binding over 100 ns. ADMET predictions showed acceptable solubility (logS = −3.899), lipophilicity (logP = 1.977), and minimal interaction with P-glycoprotein, though tissue distribution may be limited. Conclusion: Methyl angolensate exhibits selective cytotoxicity, strong AR binding, stable molecular interaction, and promising pharmacokinetic properties. These findings support its potential as a novel antiandrogenic agent and validate the traditional use of E. angolense in prostate cancer treatment.