In silico Molecular Docking Analysis of Bioactive Compounds from Tribulus terrestris targeting Renal Cancer

Abstract

Many plants have been traditionally used in the treatment of various types of diseases, including those caused by cancer; therefore, the objective of this study is to investigate whether the active ingredients found in Tribulus terrestris can either inhibit or otherwise interfere with proteins which play a role in the development of kidney cancer. A gas chromatographymass spectrometer (GC-MS) was used to analyze the methanol extract of T. terrestris. The GC-MS results showed fatty acids esters and phenolic derivatives that would likely contribute to provide therapeutic benefits of T. terrestris. In order to better understand the ability of the compounds to provide therapeutic benefits, a machine learning algorithm was designed and implemented to identify and rank candidate compounds based on their structural characteristics. Following the implementation of a machine learning algorithm to rank candidate compounds, molecular docking studies using AutoDock Vina were conducted to determine the extent to which specific phytochemicals are capable of binding to proteins related to HIF-2α, which are implicated in the development of ccRCC. The results obtained during the molecular docking studies indicate that multiple phytochemicals demonstrated favorable interaction with the target proteins and may therefore inhibit cancer-related signaling pathways. Pharmacokinetic and toxicological profiles of candidate compounds were determined via ADME-Tox analysis. Normal mode analysis (NMA) was also employed to assess the stability of protein-ligand complexes formed during the molecular docking studies. Finally, cytotoxicity testing was conducted on two human kidney cancer cell lines (Caki-1 and 786-O) using a methanolic extract of T. terrestris. Overall, T. terrestris has potential as a source of anticancer agents for the treatment of kidney cancer.