IDENTIFICATION AND SCREENING OF PLANT-BASED POTENT INHIBITORS AGAINST nSH2 DOMAIN OF PI3K OF BREAST CANCER USING DOCKING AND SIMULATION STUDIES

Abstract

Breast cancer (BC) is a critical health issue that affects countless women, and it is the second leading reason of death worldwide. The phosphatidylinositol 3 kinases (PI3Ks) constitute a group of lipid kinases that play a role in tumorigenesis, development, migration, infiltration, programmed cell death, glycogen synthesis, DNA correction and viability by the PI3K/Akt cascade. The PI3K pathway has been linked to a variety of malignancies and increases the activation rate of cancer. Here, focus was given to the study of PI3K pathway involved in BC and emphasis was given on a particular nSH2 domain that resides in the regulatory subunit of PI3K to find a potent inhibitor. A detailed pathway and interaction study was performed from KEGG pathway database and from the cystoscope. A total list of 60 compounds, comprises phytochemicals, and herbal compounds were screened based on structural similarity and eight FDA-approved drugs were considered. The docking analysis was carried over through the AutoDock software and Ligplot analysis was performed to investigate the interaction between the nSH2 domain and the potent inhibitors. To ensure the complex stability, 20 ns of simulation run was also performed on the best complexes using GROMACS. From this study, it can be concluded that Evodia fruit has the maximum stability in the catalytic region among all the listed inhibitors against the target proteins and can act as a potent inhibitor among the others.