Phenotypic screening of novel aromatic amidines against Trypanosoma cruzi
| Autor: | Silva, Marianne Rocha Simões, Gama, Aline Nefertiti Silva da, Araújo, Julianna Siciliano de, Batista, Marcos Meuser, Silva, Patrícia Bernardino da, Bahia, Maria Terezinha, Barreto, Rubem Figueiredo Sadok Menna, Pavão., Beatriz Philot, Green, Julius, Farahay, Abdelbaset A, Kumar, Arvind, Boykin, David Wilson, Soeiro, Maria de Nazaré Correia |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Zdroj: | Repositório Institucional da UFOP Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
| Popis: | The current treatment of Chagas disease (CD), based on nifurtimox and benznidazole (Bz), is unsatisfactory. In this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. Ten novel amidines were tested for their activities against bloodstream trypomastigote (BT) and amastigote forms of Trypanosoma cruzi (Y and Tulahuen strains) and their toxicities for mammalian host cells (L929 cells and cardiac cells). Seven of 10 molecules were more active than Bz against BT, with the most active compound being the diamidine DB2267 (50% effective concentration [EC50] 0.23 M; selectivity index 417), which was 28-fold more active and about 3 times more selective than the standard drug. Five of the six monoamidines were also more active than Bz. The combination of DB2267 and DB2236 in fixed-ratio proportions showed an additive effect (sum of fractional inhibitory concentrations |
| Databáze: | OpenAIRE |
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