Abstract
Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 microM, five exhibited values less than 0.40 microM, and two gave values less than 0.10 microM in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiprotozoal Agents / chemical synthesis*
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Antiprotozoal Agents / chemistry
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Antiprotozoal Agents / pharmacology*
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Benzamidines / chemical synthesis
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Benzamidines / chemistry
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Benzamidines / pharmacology
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DNA, Protozoan / metabolism
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Leishmania donovani / drug effects*
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Leishmania donovani / genetics
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Leishmania donovani / ultrastructure
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Rats
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Structure-Activity Relationship
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Terphenyl Compounds / chemical synthesis*
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Terphenyl Compounds / chemistry
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Terphenyl Compounds / pharmacology*
Substances
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Antiprotozoal Agents
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Aza Compounds
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Benzamidines
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DNA, Protozoan
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Terphenyl Compounds