Inhibition by dications of in vitro growth of Leishmania major and Leishmania tropica: Causative agents of old world cutaneous leishmaniasis

Alexa C. Rosypal, Karl A. Werbovetz, Manar Salem, Chad E. Stephens, Arvind Kumar, David W. Boykin, James E. Hall, Richard R. Tidwell

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Old World cutaneous leishmaniasis is caused by infection with Leishmania major and Leishmania tropica. Pentamidine and related dications exhibit broad spectrum antiprotozoal activity. Based on the previously reported efficacy of these compounds against related organisms, 18 structural analogs of pentamidine were evaluated for in vitro antileishmanial activity, using pentamidine as the standard reference drug for comparison. Furan analogs and reversed amidine compounds were examined for activity against L. major and L. tropica promastigotes. The most active compounds against both Leishmania species were in the reversed amidine series. DB745 and DB746 exhibited the highest activity against L. major and DB745 was the most active compound against L. tropica. Both of these compounds exhibited 50% inhibitory concentrations (IC50) below 1 nM for L. major. Ten reversed amidines were also tested for their ability to inhibit growth in an axenic amastigote model. Nine of 10 reversed amidine analogs were active at concentrations below 1 nM. These results justify further study of dicationic compounds as potential new agents for treating cutaneous leishmaniasis.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalJournal of Parasitology
Volume94
Issue number3
DOIs
StatePublished - Jun 1 2008

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amidines
Leishmania tropica
Amidines
leishmaniasis
Leishmania major
cutaneous leishmaniasis
Cutaneous Leishmaniasis
Pentamidine
furan
Growth
Inhibitory Concentration 50
inhibitory concentration 50
drug
amastigotes
promastigotes
furans
Leishmania
reference standards
drugs
In Vitro Techniques

ASJC Scopus subject areas

  • Parasitology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Inhibition by dications of in vitro growth of Leishmania major and Leishmania tropica : Causative agents of old world cutaneous leishmaniasis. / Rosypal, Alexa C.; Werbovetz, Karl A.; Salem, Manar; Stephens, Chad E.; Kumar, Arvind; Boykin, David W.; Hall, James E.; Tidwell, Richard R.

In: Journal of Parasitology, Vol. 94, No. 3, 01.06.2008, p. 743-749.

Research output: Contribution to journalArticle

Rosypal, Alexa C. ; Werbovetz, Karl A. ; Salem, Manar ; Stephens, Chad E. ; Kumar, Arvind ; Boykin, David W. ; Hall, James E. ; Tidwell, Richard R. / Inhibition by dications of in vitro growth of Leishmania major and Leishmania tropica : Causative agents of old world cutaneous leishmaniasis. In: Journal of Parasitology. 2008 ; Vol. 94, No. 3. pp. 743-749.
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