Abstract

Despite various treatments such as chemotherapy, hormonal therapy, and radiation therapy, concerns regarding the effectiveness, safety, and efficiency of older medications have driven the demand for novel therapeutic agents. Numerous microbial metabolites are used as therapeutic agents for cancer cells, either as stand-alone formulations or as conjugates with approved medicines. In the current investigation, we used in silico technologies encompassing network analysis, molecular docking, and molecular dynamics (MD) and simulation, focusing on human progesterone receptor (PGR) synthase. Molecular docking experiments revealed that iturin A exhibited the highest binding affinity to the target, with a binding affinity of −5.5 kcal/moL. Subsequently, the PGR complexed with iturin A underwent a 200 ns MD simulation in a physiological environment. The results of root mean square deviation (RMSD), root mean square fluctuations (RMSF), radius of gyration (RG), solvent accessible surface area (SASA), and hydrogen bonding illustrated that the ligand maintained a relatively constant shape throughout the simulation. In vitro studies of iturin A were performed on human breast cancer MCF-7 cells, and the results of the MTT test demonstrated an inhibitory action with an IC50 value of 42.79 μg/mL. The apoptotic effect of iturin A was studied using MCF-7 cell lines, and the results were positive with early apoptosis of 15.3%, confirming the anticancer activity of iturin A. This allowed the assessment of cell viability. This study validated the use of iturin A as an anticancer agent. The combined insights from our network analysis, in silico tests, and in vitro analyses collectively underscored the potential efficacy of iturin A in combating breast cancer.

Key words: Network pharmacology; Iturin-A; Progesterone receptor; Docking; Molecular dynamics simulation; In vitro study