Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi
Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 6–7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is...
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Veröffentlicht in: | European journal of medicinal chemistry 2016-03, Vol.111, p.46-57 |
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Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 6–7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. The present work reports the synthesis and anti-T. cruzi activities of a novel series of phthalimido-thiazoles. Some of these compounds showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in spleen cells, and the resulting structure-activity relationships are discussed. We also showed that phthalimido-thiazoles induced ultrastructural alterations on morphology, flagellum shortening, chromatin condensation, mitochondria swelling, reservosomes alterations and endoplasmic reticulum dilation. Together, these data revealed, for the first time, a novel series of phthalimido-thiazoles-structure-based compounds with potential effects against T. cruzi and lead-like characteristics against Chagas disease.
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•The anti-T. cruzi activity of 26 phthalimido-thiazoles were evaluated.•Five compounds presented better trypanocidal activity than Benznidazole.•Compound 6j was 26-fold more selective than Benznidazole.•The structural upgrade planned present positive effects on trypanocidal activity. |
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2016.01.010 |