Novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents

We have previously shown that 3-nitro-1H-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against Trypanosoma cruzi, the causative parasite of Chagas disease. More importantly, several such analogs displayed significant antichagasic activity in vivo, sup...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2014-11, Vol.87, p.79-88
Main Authors: Papadopoulou, Maria V., Bloomer, William D., Rosenzweig, Howard S., Wilkinson, Shane R., Kaiser, Marcel
Format: Article
Language:English
Subjects:
Amides - chemistry
Amides - pharmacology
Antitrypanosomal agents
Apoptosis - drug effects
Blood Platelets - drug effects
Blood Platelets - parasitology
Cells, Cultured
Chagas disease
Chagas Disease - drug therapy
Chagas Disease - parasitology
Flow Cytometry
Heteroarylamides
Heteroarylsulfonamides
Heterocyclic Compounds - chemistry
Heterocyclic Compounds - pharmacology
Humans
Imidazoles - chemistry
In Vitro Techniques
Leishmania donovani - drug effects
Leishmaniasis, Visceral - drug therapy
Leishmaniasis, Visceral - parasitology
Molecular Structure
Monocytes - drug effects
Monocytes - parasitology
Nitroimidazoles
Nitrotriazoles
Platelet Activation - drug effects
Sulfonamides - chemistry
Sulfonamides - pharmacology
Triazoles - chemistry
Trypanocidal Agents - chemistry
Trypanocidal Agents - pharmacology
Trypanosoma cruzi - drug effects
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Summary:We have previously shown that 3-nitro-1H-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against Trypanosoma cruzi, the causative parasite of Chagas disease. More importantly, several such analogs displayed significant antichagasic activity in vivo, superior to that of benznidazole, the current clinical standard. We now report the synthesis and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides (including 3-nitrotriazole-, 2- and 4-nitroimidazole-based compounds) as potential antitrypanosomal agents. All nitrotriazoles displayed significant growth inhibitory properties against T. cruzi with the most potent generating IC50 values of 1400-fold selectivity toward the parasite. The 2-nitroimidazole-based derivatives were moderately active against T. cruzi and displayed selectivity
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2014.09.045