Exploring Dandelion-Derived Phytoactive Compounds As Potential Inhibitors Of Lymphotoxin-Alpha Protein Mutants In Triple-Negative Breast Cancer

Abstract

This study aims to discover the mechanisms by which phytoactive compounds from Dandelion exert anti-breast cancer effects through in silico analysis, exploring their potential as promising therapeutic candidates against triple-negative breast cancer in particular. For this purpose, the against lymphotoxin-alpha (LT-alpha) was chosen based on their high protein-protein interaction scores. The protein sequence was retrieved from databases such as NCBI and UniProt. Structural modeling was performed using the SWISS-MODEL platform, Structural validation identified by the SAVES server and TM-align. Ligand preparations involved selecting ligands including sesquiterpenoids, sphingolipid, taraxafolin, triterpenoids, and phenol 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. The target protein LT-alpha is a protease involved in the regulation of fetal growth and TNBC. Several compounds, such as sesquiterpene lactones, phenolic acids, triterpenoids, polysaccharides, phytosterols, volatile oils, exhibit promising binding potential towards the target protein, with an affinity of -7.9 kcal/mol and rmsd scores of 21.079 and 18.688 angstroms, respectively. The results of this study provide a solid starting point for the development of the protein inhibitors and offer potential therapeutic applications across therapeutics. It provides novel insights into candidates' properties as potential LT-alpha inhibitors, highlighting molecules like alosquiterpene lactones, phenolic acids, triterpenoids, polysaccharides, phytosterols, volatile oils for further preclinical development against aggressive triple-negative breast cancer driven by this pathway pending more research.