In silico evaluation of plant-derived bioactive compounds targeting the mtor pathway in breast cancer: picroside ii as a promising natural inhibitor

Abstract

Breast cancer represents nearly 25% of all cancer diagnoses and is a complex condition comprising various subtypes that are classified based on the presence or absence of hormone receptors. The PI3K/AKT/mTOR signaling pathway plays a central role in breast cancer development, as it governs crucial cellular activities such as growth, proliferation, and survival. This pathway is frequently disrupted in hormone receptor-positive breast cancers. Though  mTOR inhibitors, such as rapamycin and its analog (rapalog), have shown promise in treatment, their clinical use is often hindered by undesirable side effects. Therefore, the development of novel inhibitors targeting the mTOR pathway is crucial. This study investigates the binding efficiency and molecular interactions of several anti-carcinogenic bioactive compounds namely Vindoline, Vincristine, Vinblastine, Picroside, And Cucurbitacin B against the mTOR complex using the Schrödinger Suite for molecular docking analysis. These compounds, derived from medicinal plants traditionally used in cancer therapies, including those in Siddha and other traditional medicine systems, have demonstrated therapeutic promise. Among the evaluated compounds, Picroside II, isolated from Picrorhiza kurroa, a medicinal herb extensively used in traditional Chinese medicine, showed the highest binding affinity (-12.134 kcal/mol) for mTOR, surpassing that of the reference inhibitor rapamycin. These results indicate that Picroside II could be a promising lead compound for further research in breast cancer therapy, with the potential to offer benefits over current mTOR inhibitors. These results indicate that Picroside II could be a promising lead compound for further research in the treatment of cancer, with the potential to provide improved efficacy compared to existing mTOR inhibitors.