Computational screening of GC-MS-derived secondary metabolites from Botryodiplodia theobromae (Lasiodiplodia theobromae) as potential ERBIN inhibitors in breast cancer

Botryodiplodia theobromae (syn. Lasiodiplodia theobromae) is an endophytic fungus with a rich resource of bioactive secondary metabolites. Its cytotoxicity towards BC cells has previously been studied. However, its mechanism of action at a molecular level is still not well understood. This study was designed to establish drug-likeness and binding affinity of GC-MS-detected B. theobromae compounds against the ERBIN PDZ domain, a stabilizer of the HER2 receptor implicated in the pathogenesis of Breast Cancer (BC). Fungal metabolites were extracted from B. theobromae using dichloromethane and analysed by Gas Chromatography-Mass Spectrometry (GC-MS) to identify the compounds. The 2D and 3D structures of these compounds were retrieved from PubChem and was evaluated for drug-likeness using Lipinski’s Rule of Five. Molecular docking was conducted with AutoDock against the ERBIN protein (PDB ID: 1MFG). LigPlot + was employed to visualize the key protein–ligand interactions for the top-scoring compounds. There were nine significant compounds identified through the application of GC-MS. Analysis using Lipinski indicated that seven compounds were drug-like. Molecular docking showed that [5-(4-Nitro-phenyl)- [1, 3, 4]oxadiazol-2-yl]-acetic acid ethyl ester had the highest affinity of binding (–8.21 kcal/mol), followed by 1,2-Benzenedicarboxylic acid, mono[2-ethylhexyl] ester (–7.59 kcal/mol). LigPlot+ interaction diagrams confirmed the presence of favourable hydrogen bonds and hydrophobic contacts with the ERBIN active site. This study emphasizes the promise of Botryodiplodia theobromae secondary metabolites as ERBIN-mediated BC development inhibitors. The combination of in vitro cytotoxic data and in silico molecular modelling is a good starting point for future research on these fungal metabolites as new anticancer drugs.