Investigating the role of phytochemicals from Euphorbia pulcherrima and Ricinus communis in modulating estradiol 17-beta -dehydrogenase 1 activity for breast cancer treatment

Abstract

Cancer, characterized by uncontrollable cell proliferation, poses a significant global health challenge, with breast cancer being one of the most prevalent and lethal forms. Despite advancements in treatment, the rising prevalence and mortality rates underscore the need for innovative therapeutic approaches. This study focuses on the first enzyme of the HSD17B family, specifically the HSD17B1 enzyme, known for its role in estrogen production and its impact on the spread of breast cancer cells. Targeting this enzyme, particularly 17-beta-Hydroxysteroid dehydrogenase type 1 (17-beta-HSD1), presents a promising avenue for treatment. Utilizing molecular docking and molecular dynamics simulations, we investigated the binding potential of phytoconstituents from Euphorbia pulcherrima and Ricinus communis on the Estradiol 17-beta-Dehydrogenase 1 enzyme. The study focuses on compounds such as Rutin, Kaempferol-3-O-Glcoside, Stigmasterol, Beta-sitosterol, and Germanicol.Kaempferol-3-O-Glucoside and Stigmasterol also show potential, emphasizing the importance of specific interactions alongside docking scores. Molecular dynamics simulations reveal varying degrees of stability among the complexes, with Kaempferol-3-O-Glucoside demonstratingstable binding configuration, Stigmasterol showing higher flexibility, and Rutin displaying moderate structural fluctuations. This integrated approach provides a comprehensive understanding ligand-protein interactions, offering valuable insights for the design and optimization of potential therapeutic compounds targeting Estradiol 17-beta-Dehydrogenase in treatment of breast cancer.