title: An in-silico investigation of anti-Chagas phytochemicals.
abstract: Over 18 million people in tropical and subtropical America are afflicted by American trypanosomiasis or Chagas disease. In humans, symptoms of the disease include fever, swelling, and heart and brain damage, usually leading to death. There is currently no effective treatment for this disease. Plant products continue to be rich sources of clinically useful drugs, and the biodiversity of the Neotropics suggests great phytomedicinal potential. Screening programs have revealed numerous plant species and phytochemical agents that have shown in-vitro or in-vivo antitrypanosomal activity, but the biochemical targets of these phytochemicals are not known. In this work, we present a molecular docking analysis of Neotropical phytochemicals, which have already demonstrated antiparasitic activity against Trypanosoma cruzi, with potential druggable protein targets of the parasite. Several protein targets showed in-silico selectivity for trypanocidal phytochemicals, including trypanothione reductase, pteridine reductase 2, lipoamide dehydrogenase, glucokinase, dihydroorotate dehydrogenase, cruzain, dihydrofolate-reductase/thymidylate-synthase, and farnesyl diphosphate synthase. Some of the phytochemical ligands showed notable docking preference for trypanothione reductase, including flavonoids, fatty-acid-derived oxygenated hydrocarbons, geranylgeraniol and the lignans ganschisandrine and eupomatenoid-6.
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: McCulley
authors.affiliation: Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA. wsetzer@chemistry.uah.edu.
authors.forename: William N
authors.initials: WN
authors.lastname: Setzer
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D003198:Computer Simulation; D006801:Humans; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D064209:Phytochemicals / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000302:isolation & purification
chemical_list: D064209:Phytochemicals; D010936:Plant Extracts; D014344:Trypanocidal Agents