Chemical constituents of Rhazya stricta as potential Aurora kinase A inhibitors for targeting HER2-negative breast cancer: an integrated in-silico and in-vitro study.

Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer is a type of breast cancer that does not overexpress the HER2 protein. In some breast cancers, overexpression of HER2 makes the cancer more aggressive. Computational-aided drug discovery (CADD) was taken as an efficient alternative to conventional methods of drug design and development. This study has also been carried out using the same drug design and development methods from Rhazya stricta; whose extracts are traditionally approved to possess anti-cancer activity while choosing Aurora Kinase A (AURKA) as our target of interest. Phytochemicals present in Rhazya stricta were found from already published literature, to be tested as potential AURKA inhibitors through molecular docking, Prime MM-GBSA, and Molecular Dynamic (MD) simulations to know about the binding energies and fluctuating stability of ligands with protein. Five out of twenty-seven screened compounds showed stable complexes and remarkable binding scores ranging between - 6.569 kcal/Mol to -5.371 kcal/Mol with the target protein so can be investigated as potential lead compounds to treat HER2-negative breast cancer. The in-silico techniques employed successfully identified phytochemicals with potent human AURKA inhibitory properties. Compounds (6), (8), (5), (4), (1) as AURKA inhibitors have the potential to block AURKA by targeting p53 tumor-suppressing protein to prevent the further development of tumors. The MTT assay was performed to confirm the cell viability, cell inhibition, and cytotoxicity of the phytochemicals present in the plant extract.