title: In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum.
abstract: Canine leishmaniasis caused by Leishmania infantum is enzootic in the North American foxhound population. Currently available chemotherapy for canine leishmaniasis is not completely effective and relapses are common in treated dogs. Pentamidine and related aromatic diamidines possess broad spectrum antiprotozoal activity. The in vitro antileishmanial activities of 35 aromatic cationic molecules were determined, using pentamidine as the reference drug. The compounds were examined for activity against promastigotes of L. infantum isolated from a foxhound from Virginia. The compounds most active against Leishmania parasites were reversed amidines. Compound 9, a reversed amidine, exhibited the highest activity against L. infantum, with a 50% inhibitory concentration (IC(50)) of 0.0042 microM compared with 14.2 microM for pentamidine. Antileishmanial activities of nine compounds were at least 1000-fold higher relative to the reference drug. Results from this study indicate that several pentamidine-related compounds warrant further investigation as possible new agents for the treatment of canine leishmaniasis.
authors.affiliation: School of Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. arosypal@email.unc.edu
authors.forename: Alexa C
authors.initials: AC
authors.lastname: Rosypal
authors.forename: James E
authors.initials: JE
authors.lastname: Hall
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bakunova
authors.forename: Donald A
authors.initials: DA
authors.lastname: Patrick
authors.forename: Stanislav
authors.initials: S
authors.lastname: Bakunov
authors.forename: Chad E
authors.initials: CE
authors.lastname: Stephens
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.forename: Richard R
authors.initials: RR
authors.lastname: Tidwell
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004283:Dog Diseases / Q000469:parasitology*; D004285:Dogs; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000276:immunology* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000662:veterinary*; D015394:Molecular Structure
chemical_list: D000981:Antiprotozoal Agents