title: In vitro and in vivo activity of benzo[c]phenanthridines against Leishmania amazonensis.
abstract: Seven benzo[c]phenanthridines, synthetic or isolated from Zanthoxylum rhoifolium root bark, were evaluated against Leishmania amazonensis axenic amastigotes. Five of them were considered leishmanicidal, with IC50 values ranging from 0.03 to 0.54 µM, and were evaluated on intramacrophagic amastigotes of L. amazonensis. Chelerythrine displayed the best activity (IC50=0.5 µM), which was in the same range as the reference compound amphotericin B (IC50=0.4 µM). In vivo studies with chelerythrine, avicine, and fagaridine on a model of mice cutaneous leishmaniasis resulted in the identification of fagaridine as the most active compound. Fagaridine decreased the parasitic burden more than 50% at the 3rd and 6th weeks after the end of treatment.
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Denis
authors.initials: D
authors.lastname: Castillo
authors.affiliation: Institut de Recherche pour le Développement (IRD), Mission IRD, Lima, Peru.
authors.forename: Michel
authors.initials: M
authors.lastname: Sauvain
authors.affiliation: Institut de Recherche pour le Développement (IRD), Laboratoire Pharmadev, Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Rivaud
authors.affiliation: Institut de Recherche pour le Développement (IRD), Laboratoire Pharmadev, Toulouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Jullian
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D010617:Phenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D053119:Benzophenanthridines; D010617:Phenanthridines; D010936:Plant Extracts; C518455:fagaridine; C016299:chelerythrine