Systems Pharmacology Approach to Determine the Natural Compound s Antagonist Effect for Treatment of Gynecological Cancer

Abstract

Cancer arises when cells break free from the normal regulatory mechanisms that control their growth and spread. Gynaecological cancers, affecting the reproductive organs including the cervix, ovaries, uterus, fallopian tubes, and vagina, exhibit distinct characteristics that require specialized treatment approaches. In this study, the roles of key oncogenic genes NEK2, PIK3CA, and FBXW7 in gynaecological cancer progression were explored. Through gene expression analysis and mutational profiling, it was found that structural and functional alterations in these genes, particularly mutations in FBXW7 and PIK3CA, inhibit drug binding, thus complicating existing treatment options. Mutation profiling was employed to identify these structural changes in the genes. Further, toxicity and QSAR (Quantitative Structure-Activity Relationship) analyses demonstrated that natural marine-derived compounds exhibited lower toxicity and enhanced efficacy compared to conventional drugs. newlineMolecular docking and density functional theory (DFT) studies were performed to assess the interactions between these natural compounds and oncogenes. These analyses confirmed that the compounds showed strong interactions with NEK2 and PIK3CA, newlineinhibiting their function effectively. DFT calculations also provided insights into the stabilization and energy calculations of the drug-protein interactions, identifying the most stable compound based on the lowest energy state. Additionally, molecular dynamics simulations were used to validate the stability and dynamic behavior of the drug-protein interactions. newline