Study of Glabranin as an Inhibitor Against Prostate Cancer: Molecular Docking, Molecular Dynamics Simulation, MM-PBSA Calculation and QSAR Prediction.

Prostate cancer is the World's second most frequent malignancy, with the fifth-highest male mortality rate. In advanced prostate cancer patients, point mutations such as T877A and W741L are prevalent, imparting treatment resistance and hence promoting cancer development. The emergence of drug resistance in prostate cancer necessitates the development of suitable ligands to allow for stronger interactions with the receptors, which can inhibit cancer progression. The present study focuses on flavonoids produced by plants, which may act as inhibitors of point mutations like T877A and W741L in prostate cancer. This research was conducted using an in-silico method where the compound Glabranin and its derivatives were virtually screened to identify potential drugs for combating such point mutations. Thirty-five Molecular Dockings were performed to find the ligand-receptor complexes with the lowest binding energy. Moreover, employing a variety of tools, ligands were evaluated for drug-likeness and toxicity, indicating a promising drug candidate. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, eight structures were subjected to a 100 ns Molecular Dynamics simulation. A QSAR analysis was also performed based on the simulation findings. In this study, it was revealed that GlaMod2 phytocompound was effective against T877A and W741L mutations in prostate cancer. It was observed that the phytocompound was stable and had potential properties for the development of a novel drug to combat prostate cancer and drug resistance This phytocompound may therefore be effective in the development of prostate cancer inhibitors for patients with mutant androgen receptors. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01134-3.