Compounds from Morchella esculenta as Potential Inhibitors of RNA-Binding Protein La in Ovarian Cancer: A Molecular Modeling and Quantum Mechanics Approach

Abstract

Ovarian cancer (OC) is implicated in most gynecological cancer-related deaths. Currently, the primary treatments for OC are surgery and chemotherapy using platinum-based drugs to induce remission. However, OC recurs in 70-80% of patients within two years, which usually results in the death of most OC patients. La protein is significantly expressed in various malignant tumors, including OC. Previous studies reported that OC patients have significantly higher levels of La protein expression in their serum than healthy individuals, which is related to the poor response to platinum-based chemotherapy. Inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention in treating OC. Extract from Morchella esculenta (morel mushroom) has been reported to contain anti-cancer properties, but no study has reported the interaction of its bioactive compounds with La protein in OC. This study examines the interaction of La protein with some bioactive compounds of Morchella esculenta, as well as their pharmacokinetics and thermochemical properties using structural bioinformatics and advanced theoretical chemistry techniques. Molecular modeling techniques incorporating molecular docking, free energy calculation, MD simulation, drug-likeness, and quantum chemical calculations, including the global hybrid and long-range corrected density functional theory approximations, were employed in this study. Thus, the results identify hits compounds from morchella esculanta, which could serve as a starting for the development of novel LA protein inhibitors for OC therapeutics.