Pharmacokinetic Properties of Bioactive Compounds of Aloe vera against Pregnancy-Associated Plasma Protein A (PAPP-A) inducing Triple-Negative Breast Cancer

Abstract

This study aims to discover the mechanisms by which phytoactive compounds from Aloe vera 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 pregnancy associated plasma protein-A (PAPP-A) 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 aloenin, aloe-emodin, aloeresin D, aloesin, aloiniside A, anthraquinones, naphthoquinones, and phenol, phytosterol, and terpenoids 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 PAPP-A is a protease involved in the regulation of fetal growth and TNBC. Several compounds, such as aloe-emodin, aloeresin D, phenol, anthraquinone, naphthoquinones, and aloiniside A, 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 PAPP-A inhibitors and offer potential therapeutic applications across therapeutics. It provides novel insights into candidates' properties as potential PAPP-A inhibitors, highlighting molecules like aloenin, aloesin and anthraquinones for further preclinical development against aggressive triple-negative breast cancer driven by this pathway pending more research.