In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum.
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.
Rosypal
Alexa C
AC
School of Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. arosypal@email.unc.edu
Hall
James E
JE
Bakunova
Svetlana
S
Patrick
Donald A
DA
Bakunov
Stanislav
S
Stephens
Chad E
CE
Kumar
Arvind
A
Boykin
David W
DW
Tidwell
Richard R
RR
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
D000981:Antiprotozoal Agents