Computational Validation of Tecomella undulata Bark as a Source of Anti-Filarial Leads Targeting UDP-Galactopyranose Mutase.

Lymphatic filariasis remains a major neglected tropical disease and there is an urgent need for parasite-specific therapeutic targets. The enzyme UDP-galactopyranose mutase (UGM) is essential for galactofuranose biosynthesis in Brugia malayi and is absent in humans, which makes it a promising drug target. In this study, we investigated phytochemicals from the bark of Tecomella undulata to find potential drug candidates against B. malayi UGM using an in silico approach. The structure of the target protein was predicted using the Alphafold model, and the active site was predicted using the combination of PrankWeb, DoGSiteScorer, and FTMap servers and further supported by superposition with a homologous experimentally determined UGM structure. Forty phytochemicals of T. undulata bark were screened by molecular docking using AutoDock Tools. Docking analysis showed Dehydrotectol (- 11.73 kcal/mol), Daucosterol (- 11.35 kcal/mol), urs-12-ene (- 10.87 kcal/mol), β-sitosterol (- 10.72 kcal/mol), and betulinic acid (- 10.47 kcal/mol) are the top-scoring ligands. Based on predicted binding free energy and interaction with key catalytic residues of UGM, Daucosterol was selected for molecular dynamics simulation using the GROMACS package. MD analysis and MM/PBSA calculations supported the thermodynamic stability of the docked complex. ADMET predictions indicated acceptable drug-likeness and low toxicity of several phytoconstituents of T. undulata bark. This study provides computational evidence supporting T. undulata bark phytochemicals can be a new drug formulation against B. malayi.