Integrated structure model-based virtual screening approaches identified anti-cancer agents against prostate cancer by targeting MAOB protein

Background Flavin monoamine oxidase gene encodes a protein (MAOB) that forms a part of the flavin monoamine oxidase family in the outer membrane of mitochondria. It plays a role in the tissue metabolism of neuroactive and vasoactive amines as well as the oxidative deamination of xenobiotic and biogenic amines. However, overexpression of the receptor reduced apoptosis in cells, resulting in the progress of prostate sarcoma. Therefore, various kinds of MAOB antagonists are often used to fix an apoptosis mechanism that makes it hard to get rid of cancer from live tissues. Moreover, chemical compounds that have been discovered to be MAOB inhibitors to date exhibit side effects that are causing problems in chemotherapy treatment. The study aims to discover new purchasable compound that induces apoptosis by allowing caspases to operate at their maximum efficiency and is low toxic. Methods With the assistance of virtual screening, molecular docking, and molecular dynamics simulation (MD), a structure-based pharmacophore model of the protein active site cavity was made. Twenty hits were found, and then a molecular docking strategy was used to choose four molecules to study in more depth. MD simulations were used to check the stability of the four compounds, and they were all shown to be stable when bound to the target protein. Results Four newly discovered compounds, included with ZINC ID Such as ZINC12143050, ZINC08301324, ZINC16743012, and ZINC64165826 with binding scores of − 11.7, − 11.4, − 11.2 and − 11.1 kcal/mol, respectively, may serve as lead compounds for the treatment of prostate cancer associated with MAOB; however, further evaluation through wet lab is needed to determine the compounds effectiveness. Conclusion A structure-based model was initially developed, followed by molecular docking, ADMET analysis, and MD simulation. The top four natural compounds identified in the A-to-Z virtual screening process could serve as lead molecules in the fight against prostate cancer.