title: In-silico investigation of antitrypanosomal phytochemicals from Nigerian medicinal plants.
abstract: BACKGROUND
  Human African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment.
  
  
  METHODS
  A molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14α-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4' epimerase (TbUDPGE), and ornithine decarboxylase (TbODC).
  
  
  RESULTS
  This study revealed that triterpenoid and steroid ligands were largely selective for sterol 14α-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4' epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins.
  
  
  CONCLUSIONS
  This in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations.
authors: Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama, USA. wsetzer@chemistry.uah.edu
authors: William N
authors: WN
authors: Setzer
authors: Ifedayo V
authors: IV
authors: Ogungbe
mesh_terms: D017954:Africa South of the Sahara; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D056004:Molecular Dynamics Simulation; D010946:Plants, Medicinal / Q000737:chemistry*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000235:genetics*
chemical_list: D000981:Antiprotozoal Agents; D015800:Protozoan Proteins