In-silico strategies for probing fatty acids-based inhibitors from palm Kernel (Elaeis guineensis) Oil against Aldo-Keto Reductase 1C3 (AKR1C3)

Aldo-Keto Reductase 1C3 (AKR1C3) is a vital human enzyme involved in the NADPH-dependent reduction of carbonyl groups in various steroids and prostaglandins. Its overexpression is linked to cancers such as breast, endometrial, and prostate. This study investigated the potential effects of fatty acids from Palm Kernel (Elaeis guineensis) oil on AKR1C3 using GC-MS analysis and in-silico methods. We evaluated Gas Chromatography-Mass Spectrometry (GC-MS) data, physicochemical properties, lipophilicity, pharmacokinetics, Lipinski's drug-likeness, and toxicity of the molecules. Molecular docking studies with AKR1C3 were conducted using Autodock Vina software, followed by validation using the MM/GBSA method and stability assessment through 100 ns molecular dynamics (MD) simulations with Desmond software. Findings revealed that 9-Octadecenoic acid (Z)-2-hydroxy-1-(hydroxymethyl) ethyl ester (-8.2 kcal/mol) exhibited superior binding energies compared to the control ligand, 3-phenoxybenzoic acid (-8.1 kcal/mol). MM/GBSA calculations demonstrated favorable binding affinities, and superimposed RSMD (0.878 Å) poses of ligands showed minimal deviation. Two of the complexes were more stable throughout the 100 ns simulation period, and test compounds displayed satisfactory drug-likeness, physicochemical properties, and toxicity profiles. These promising results suggest further in vivo and in vitro exploration of the lead compounds as potential drug candidates targeting AKR1C3 in hormone-dependent cancers.