Exploration of rutin derivatives as potential inhibitors of prostate cancer signaling pathways: A comprehensive in-silico study

Prostate cancer is a widespread health issue that affects men worldwide. It is one of the most common forms of cancer, and its development is influenced by a combination of hereditary, epigenetic, environmental, age, and lifestyle factors. Given that it is the second most common cause of cancer-related deaths in men, it is crucial to comprehend its complex facets. Present research especially targets the 3-kinase/protein kinase B, Epidermal Growth Factor Receptor, and extracellular signal-related kinase pathways, which are known to be significantly involved in prostate cancer progression. Here, Rutin derivatives were screened against selected prostate cancer targets. Molecular docking was performed to identify favorable interactions and the most promising compound. Further, Density functional theory, pharmacokinetics, Molecular dynamics simulation, principal component analysis, free energy landscape analysis, and Molecular Mechanics Poisson-Boltzmann Surface Area provided additional insights into selecting the best drug candidate. Among all the selected rutin derivatives, RU4b1 has potent inhibitory action. We also performed predictive analysis to identify the distinct metabolic sites within the structure of RU4b1. RU4b1 also exhibits drug-like properties and potent antioxidant activity. The findings were also compared with standard drugs and reference molecules of the respective proteins, and it is noteworthy that RU4b1 exhibited superior action compared to the standard drugs and reference molecules. This study aims to contribute valuable insights into developing targeted therapies for prostate cancer, emphasizing the potential of rutin derivatives as effective anti-cancer agents.