Pre-clinical study of the bioactive compound Asiaticoside against the proteins inducing human mammary carcinoma using molecular docking and ADME analysis

Abstract

The objective of this study is to identify the pharmacokinetics properties of a bioactive compound of asiaticoside and its effects on breast cancer inducing proteins. For this purpose, the proteins were chosen based on their high protein-protein interaction scores. The protein sequences were retrieved from databases such as NCBI and UniProt. Structural modeling was performed using the SWISS-MODEL platform, including the construction of both wild-type and mutant protein structures. Structural validation identified by the SAVES server and TM-align. Ligand preparations involved selecting Asiaticoside from the ChEBI database and filtering for specific criteria. Protein-ligand docking analysis was carried out using the PyRx program. ADME analysis performed by SwissADME. In the protein 3D-modeling analysis, the wild-type proteins, ATM and ERBB2, showed good stability, while the mutants L115R, G138R, and R940W also maintained stability with minimal structural changes. However, in BRCA1 and BRCA2, the mutants M48R and W2626R showed slight decreases in stability compared to the wild type. In the docking analysis with asiaticoside, the wild-type proteins generally exhibited favorable interactions, while some mutants showed slightly weaker binding affinities. Overall, asiaticoside showed promising potential for its anti-inflammatory, anti-tumor, and wound-healing properties. In conclusion, the asiaticoside, determined to be a drug-friendly molecule, exhibited the highest binding energy among the compounds analyzed in molecular docking. Its ability to penetrate the blood-brain barrier makes it a recommended treatment option for breast cancer.