A comparative study of Bazedoxifene, Exemestane, Fulvestrant, Raloxifene, Tryprostatin A, and Vorinostat compounds as potential inhibitors against breast cancer through molecular docking, and molecular dynamics simulation

Abstract

Breast cancer is one of the most common cancers and topmost cause of mortality among women in both developed and developing countries. Currently available potent drugs for breast cancer exhibit adverse effects, which may be caused as a result why breast cancer-specific drugs are found to be ineffective for patients. In this study, we exploited the interaction of six potential drug compounds (Bazedoxifene, Exemestane, Fulvestrant, Raloxifene, Tryprostatin A, and Vorinostat) with three breast cancer associated proteins such as poly (ADP-ribose) polymerase-1; PARP1 (PDB ID: 5HA9) cyclin-dependent kinase 2; CDK2 (PDB ID: 6GUE), and phosphatidylinositol 3-kinases alpha; PI3Kα (PDB ID: 7K6O) using molecular docking studies. Docking results indicate that Raloxifene was shown to be the most potent inhibitor of 5HA9 protein with two hydrogen bond interactions and possesses best binding affinity of −12.3 kcal/mol. The compound Fulvestrant shows three hydrogen bond interactions and has the best binding affinity of −10.2 kcal/mol and exhibits to be the most potent inhibitor of 6GUE protein. Raloxifene indicated best binding affinity of −10.6 kcal/mol and showed to be the most potent inhibitor of 7K6O protein with two hydrogen bond interactions. Molecular dynamics simulations of 5HA9-Raloxifene, 6GUE-Fulvestrant, and 7K6O-Raloxifene were executed for 100 ns through which root mean square deviation (RMSD), root mean square fluctuation (RMSF), the number of hydrogen bonds, radius of gyration, and interaction energy was computed. The obtained results indicate that the compounds Raloxifene, and Fulvestrant can be useful for treatment of breast cancer.