Abstract
3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Cell Line
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Chagas Disease / drug therapy*
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Chagas Disease / parasitology
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Dose-Response Relationship, Drug
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Methanol / analogs & derivatives
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Methanol / chemistry
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Methanol / pharmacology*
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Mice
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Mice, Inbred BALB C
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Molecular Structure
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Parasitic Sensitivity Tests
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Rats
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Structure-Activity Relationship
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Triazoles / chemistry*
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Trypanocidal Agents / chemical synthesis
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Trypanocidal Agents / chemistry
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Trypanocidal Agents / pharmacology*
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Trypanosoma brucei rhodesiense / drug effects*
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Trypanosoma cruzi / drug effects*
Substances
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Amides
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Triazoles
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Trypanocidal Agents
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Methanol