Sanggenon C from Morus alba as a promising Bcl-2 inhibitor: a molecular docking study targeting apoptosis in lung cancer
Abstract
Bcl-2 overexpression is a key driver of apoptosis evasion and chemoresistance in lung cancer. Morus alba L. harbors bioactive phytochemicals with reported anticancer properties, yet their binding potential against Bcl-2 remains computationally unevaluated. This study aims to assess the binding affinity and interaction profiles of five M. alba-derived compounds—sanggenon C, morusin, albanol B, rutin, and kuwanon C—against Bcl-2 using molecular docking. Molecular docking was performed using AutoDockTools® (v1.5.7) with the Bcl-2 crystal structure (PDB ID: 6O0K) and venetoclax as the reference ligand. Binding free energy (ΔG), binding site similarity (%BSS), and hydrogen bond interactions were analyzed. Redocking yielded an RMSD of 1.41 Å, confirming protocol validity. Sanggenon C exhibited the most favorable binding profile (ΔG = −8.46 kcal/mol; %BSS = 81.25%), sharing 13 of 16 key residues with venetoclax, including Phe112, Val156, Met115, Phe153, Arg146, and Gly145, with three hydrogen bonds predominantly within the optimal range. These findings establish a computational basis for prioritizing sanggenon C as a Bcl-2 inhibitor lead from M. alba, warranting further validation through ADMET profiling, molecular dynamics simulation, and in vitro cytotoxicity and apoptosis assays in lung cancer cell models.
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