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

doi:10.1016/j.vetpar.2007.01.005

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

Chemistry and Physics

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Pages (from-to)	207-216
Number of pages	10
Journal	Veterinary Parasitology
Volume	145
Issue number	3-4
DOIs	https://doi.org/10.1016/j.vetpar.2007.01.005
State	Published - Apr 30 2007

Keywords

Antileishmanial activity
Aromatic diamidines
In vitro
Leishmania infantum
Pentamidine

ASJC Scopus subject areas

Parasitology
veterinary(all)

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10.1016/j.vetpar.2007.01.005

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@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.}",

note = "Funding Information: This work was supported by a grant from the Bill and Melinda Gates Foundation to R.R.T. and the contribution of A.C.R was supported by National Institute of General Medical Sciences GM 00678. A.C.R. is a postdoctoral fellow with the SPIRE (Seeding Postdoctoral Innovators in Research and Education) postdoctoral training program. The authors gratefully acknowledge Dr. Reto Brun from the Swiss Tropical Institute, Basel, Switzerland, for providing cytotoxicity data. We thank Dr. David S. Lindsay from the Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, for his gift of the LIVT-1 strain of L. infantum .",

year = "2007",

month = apr,

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.

N1 - Funding Information: This work was supported by a grant from the Bill and Melinda Gates Foundation to R.R.T. and the contribution of A.C.R was supported by National Institute of General Medical Sciences GM 00678. A.C.R. is a postdoctoral fellow with the SPIRE (Seeding Postdoctoral Innovators in Research and Education) postdoctoral training program. The authors gratefully acknowledge Dr. Reto Brun from the Swiss Tropical Institute, Basel, Switzerland, for providing cytotoxicity data. We thank Dr. David S. Lindsay from the Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, for his gift of the LIVT-1 strain of L. infantum .

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

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SN - 0304-4017

VL - 145

SP - 207

EP - 216

JO - Veterinary Parasitology

JF - Veterinary Parasitology

IS - 3-4

ER -

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

Abstract

Keywords

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