In silico elucidation and network pharmacology analysis of phytochemicals from Elephantorrhiza elephantina and Pentanisia prunelloides for antitubercular activity

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, exacerbated by drug-resistant strains. Phytochemicals, bioactive compounds from plants, offer a promising avenue for new drug development due to their diverse biological activities. This study focuses on two traditional medicinal plants, Elephantorrhiza elephantina and Pentanisia prunelloides, to identify potential anti-tuberculosis compounds. The compounds were initially evaluated for drug-likeness, followed by ADMET (absorption, distribution, metabolism, excretion, and toxicity) screening. Five compounds meeting these criteria were selected for further analysis. The 3D structures of these compounds were analyzed using PharmMapper to identify potential protein targets, focusing on those relevant to Mycobacterium tuberculosis. Protein-protein interaction networks were analyzed using STRING and Cytoscape to identify key hub genes. Additionally, KEGG pathway analysis was conducted with KOBAS to elucidate the biological processes, molecular functions, and cellular components involved. Homology modeling was performed using ITASSER to predict the 3D structure of target proteins. Finally, molecular docking studies were carried out to evaluate the binding interactions between the selected compounds and the MurF protein of Mycobacterium tuberculosis, followed by molecular dynamics simulations to assess the stability and conformational changes of the resulting protein-ligand complex over time. Among the compounds, arabinose (CID439195) demonstrated the strongest binding affinity to MurF, suggesting its potential as an anti-TB agent. These findings suggest that Elephantorrhiza elephantina and Pentanisia prunelloides hold significant potential for the development of new anti-tuberculosis therapies. This study underscores the importance of integrating computational approaches in drug discovery and highlights the promising role of phytochemicals in addressing global health challenges such as tuberculosis.