Abstract
Diamidine-containing compounds have a long history of use in the treatment of African trypanosomiasis and leishmaniasis. The discovery that diamidine prodrugs possess in vivo antimicrobial activity when administered orally has led to a renewed interest in this class of compounds for the treatment of parasitic infections. In this review, the selectivity of diamidines against trypanosomes, Leishmania and Plasmodium is rationalized through mechanism-of-action studies. An overview of the antiprotozoal activities of newer diamidines and diamidine prodrugs is also presented, along with a summary of the progress made toward the clinical development of new diamidines for use against these parasitic diseases.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antimalarials / pharmacology*
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Antimalarials / therapeutic use
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Antiprotozoal Agents / pharmacology*
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Antiprotozoal Agents / therapeutic use
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Benzamidines / metabolism*
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Benzamidines / pharmacology
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Benzamidines / therapeutic use
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Chagas Disease / drug therapy
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Clinical Trials as Topic
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Drug Evaluation, Preclinical
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Humans
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Leishmania / drug effects
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Leishmania / growth & development
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Leishmaniasis / drug therapy
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Malaria, Falciparum / drug therapy
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Pentamidine / analogs & derivatives
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Pentamidine / pharmacology*
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Pentamidine / therapeutic use
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / growth & development
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Prodrugs / pharmacology*
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Prodrugs / therapeutic use
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Trypanocidal Agents / pharmacology*
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Trypanocidal Agents / therapeutic use
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Trypanosoma brucei gambiense / drug effects
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Trypanosoma brucei gambiense / growth & development
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Trypanosoma cruzi / drug effects
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Trypanosoma cruzi / growth & development
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Trypanosomiasis, African / drug therapy
Substances
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Antimalarials
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Antiprotozoal Agents
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Benzamidines
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Prodrugs
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Trypanocidal Agents
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Pentamidine
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furamidine
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pafuramidine