Breast cancer still ranks among the top causes of death globally; therefore, new therapeutic agents are urgently needed. Microbe-derived bioactive compounds present great promise for novel drug discovery. Considering this, the study aims to evaluate their binding affinity, efficacy, bioavailability, and toxicity against key breast cancer target proteins. Molecular docking was performed on 80 bacterial compounds against six breast cancer targets (Human Epidermal Growth Factor Receptor 2 ( HER2 ), Estrogen Receptor Alpha ( ERα ), B-Cell Lymphoma 2 ( BCL2 ), Breast Cancer Gene 1 ( BRCA1 ), Breast Cancer Gene 2 ( BRCA2 ), and Peroxisome Proliferator–Activated Receptor Gamma ( PPARG )). Lead compounds were identified through molecular docking, the Lipinski rule of five, and toxicity profiling. Molecular dynamics simulations assessed the stability and dynamics of top ligand–protein complexes. In addition, a comparative analysis against known phytochemicals or drugs for breast cancer was performed. Eighteen microbial compounds showed strong binding affinities with multiple proteins. Marfuraquinocin A and Marfuraquinocin D were identified as promising candidates due to their favorable pharmacokinetic and safety profiles. Molecular dynamics simulations confirmed the structural stability of the top docked complexes, with minimal root mean square deviation fluctuations. Besides, comparative evaluation showed significant differences in binding affinities between microbial bioactives and known phytochemicals or drugs. The results suggest that microbial bioactives, particularly Marfuraquinocin A and Marfuraquinocin D, can potentially be effective breast cancer inhibitors. Future in vitro and in vivo experiments are recommended to confirm their therapeutic effectiveness and safety.
Joy et al. (Fri,) studied this question.