Introduction: Ovarian cancer is a serious disease with high incidence and mortality in women, despite advances in surgical and medical therapies. Continuous efforts to develop safer and more effective treatments are crucial. The aim of this study was to explore the potential of 5,7-dihydroxy-3(R)-methylphthalide against ovarian cancer. Methods: This study utilized a bioinformatics approach with network pharmacology to collect active compounds and genes related to ovarian cancer, predict targets, perform network analysis, gene and pathway enrichment, molecular docking and molecular dynamics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) prediction. Results: The bioinformatics approach revealed that the SRC protein was the most promising target among 28 potential target genes related to ovarian cancer influenced by the active compound. Molecular docking results indicated that the compound formed major hydrogen bond interactions with amino acid residues and exhibited relatively low binding energy values, indicating strong binding affinity. Molecular dynamics simulations confirmed the stability of the protein and ligand over 100 ns. MM-PBSA (Poisson-Boltzmann Surface Area Molecular Mechanics) analysis indicated lower binding energy for the compound. ADMET analysis indicated that the evaluated compounds did not violate the Lipinski, Ghose, Veber, and Egan rules, considering that the formulation changes showed no indication of cytotoxicity, mutagenicity, hepatotoxicity, neurotoxicity, cardiotoxicity, or immunotoxicity. Conclusion: The compound 5,7-dihydroxy-3(R)-methylphthalide has potential compared to its native ligand (1BU) and epirubicin as a control drug in targeting the SRC protein in ovarian cancer. Further in vitro and in vivo evaluation is needed to validate the activity.
Ananto et al. (Thu,) studied this question.