Network pharmacology and molecular docking identify eugenol as a lead compound targeting visceral leishmaniasis pathways with nanotechnology-driven drug design and nanoscale interaction analysis

Abstract

Visceral leishmaniasis remains a critical global health concern, necessitating the development of novel therapeutic agents. In this study, a network pharmacology and molecular docking approach is used to identify potential antileishmanial phytochemicals from four traditional Indian medicinal plants: Cassia fistula, Ceriops tagal, Avicennia paconiifolius, and Mimosa panicula. A total of 256 phytochemicals are retrieved from the IMPPAT database and screened based on ADME and drug-likeness criteria, narrowing the pool to 34 compounds. A Venn analysis identified 4 compounds shared among at least two plant species, suggesting synergistic therapeutic relevance. The predicted targets are intersected with visceral leishmaniasis-associated genes, revealing 27 shared proteins which formed a highly connected protein–protein interaction (PPI) network. GO and KEGG enrichment highlighted pathways related to inflammation, immune response, and oxidative stress. Molecular docking studies confirmed that Eugenol binds to the same active site as the co-crystallized ligand in the target protein 6TUU, with significant structural overlap and conserved interactions. These findings propose Eugenol as a promising ant parasitic agent with potential to modulate visceral leishmaniasis-relevant pathways. Furthermore, nanotechnology-based approaches enable nanoscale evaluation of ligand–protein interactions, improve drug delivery potential, and enhance the identification of bioactive compounds with higher specificity and therapeutic efficiency against visceral leishmaniasis.