In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum

Alexa C. Rosypal, James E. Hall, Svetlana Bakunova, Donald A. Patrick, Stanislav Bakunov, Chad E. Stephens, Arvind Kumar, David W. Boykin, Richard R. Tidwell

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (IC50) of 0.0042 μM compared with 14.2 μM 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.

Original languageEnglish (US)
Pages (from-to)207-216
Number of pages10
JournalVeterinary Parasitology
Volume145
Issue number3-4
DOIs
StatePublished - Apr 30 2007

Fingerprint

Leishmania infantum
Pentamidine
leishmaniasis
amidines
Leishmaniasis
Amidines
dogs
Canidae
aromatic compounds
inhibitory concentration 50
Inhibitory Concentration 50
promastigotes
drugs
Leishmania
relapse
drug therapy
Pharmaceutical Preparations
Parasites
parasites
In Vitro Techniques

Keywords

  • Antileishmanial activity
  • Aromatic diamidines
  • In vitro
  • Leishmania infantum
  • Pentamidine

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)

Cite this

In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum. / Rosypal, Alexa C.; Hall, James E.; Bakunova, Svetlana; Patrick, Donald A.; Bakunov, Stanislav; Stephens, Chad E.; Kumar, Arvind; Boykin, David W.; Tidwell, Richard R.

In: Veterinary Parasitology, Vol. 145, No. 3-4, 30.04.2007, p. 207-216.

Research output: Contribution to journalArticle

Rosypal, AC, Hall, JE, Bakunova, S, Patrick, DA, Bakunov, S, Stephens, CE, Kumar, A, Boykin, DW & Tidwell, RR 2007, 'In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum', Veterinary Parasitology, vol. 145, no. 3-4, pp. 207-216. https://doi.org/10.1016/j.vetpar.2007.01.005
Rosypal, Alexa C. ; Hall, James E. ; Bakunova, Svetlana ; Patrick, Donald A. ; Bakunov, Stanislav ; Stephens, Chad E. ; Kumar, Arvind ; Boykin, David W. ; Tidwell, Richard R. / In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum. In: Veterinary Parasitology. 2007 ; Vol. 145, No. 3-4. pp. 207-216.
@article{40fe190c3eea410e83fd4f70050f84ea,
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 (IC50) of 0.0042 μM compared with 14.2 μM 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.",
keywords = "Antileishmanial activity, Aromatic diamidines, In vitro, Leishmania infantum, Pentamidine",
author = "Rosypal, {Alexa C.} and Hall, {James E.} and Svetlana Bakunova and Patrick, {Donald A.} and Stanislav Bakunov and Stephens, {Chad E.} and Arvind Kumar and Boykin, {David W.} and Tidwell, {Richard R.}",
year = "2007",
month = "4",
day = "30",
doi = "10.1016/j.vetpar.2007.01.005",
language = "English (US)",
volume = "145",
pages = "207--216",
journal = "Veterinary Parasitology",
issn = "0304-4017",
publisher = "Elsevier",
number = "3-4",

}

TY - JOUR

T1 - In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum

AU - Rosypal, Alexa C.

AU - Hall, James E.

AU - Bakunova, Svetlana

AU - Patrick, Donald A.

AU - Bakunov, Stanislav

AU - Stephens, Chad E.

AU - Kumar, Arvind

AU - Boykin, David W.

AU - Tidwell, Richard R.

PY - 2007/4/30

Y1 - 2007/4/30

N2 - 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 (IC50) of 0.0042 μM compared with 14.2 μM 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.

AB - 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 (IC50) of 0.0042 μM compared with 14.2 μM 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.

KW - Antileishmanial activity

KW - Aromatic diamidines

KW - In vitro

KW - Leishmania infantum

KW - Pentamidine

UR - http://www.scopus.com/inward/record.url?scp=33947249443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947249443&partnerID=8YFLogxK

U2 - 10.1016/j.vetpar.2007.01.005

DO - 10.1016/j.vetpar.2007.01.005

M3 - Article

VL - 145

SP - 207

EP - 216

JO - Veterinary Parasitology

JF - Veterinary Parasitology

SN - 0304-4017

IS - 3-4

ER -