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Molecules 2017, 22(5), 709; doi:10.3390/molecules22050709

Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.

1
Laboratorio de Moléculas Bioactivas, CENUR Litoral Norte, Universidad de la República, Ruta 3 (km 363), Paysandú, C.P. 60000, Uruguay
2
Centro Para el Desarrollo de la Investigación Científica (CEDIC/FMB/Diaz Gill Medicina Laboratorial), Asunción, C.P. 1255, Paraguay
3
Grupo de Química Medicinal-Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Montevideo, C.P. 11400, Uruguay
4
Sección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo, C.P. 11400, Uruguay
5
Cell Biology of Neural Development Laboratory, Institut Pasteur de Montevideo, Montevideo, C.P. 11400, Uruguay
6
Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, C.P. 04510, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Cornelis J. Van der Schyf
Received: 21 March 2017 / Revised: 23 April 2017 / Accepted: 25 April 2017 / Published: 7 May 2017
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
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Abstract

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM–25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity. View Full-Text
Keywords: anti-T. cruzi and anti-Leishmania spp. activity; arylidene ketones; thiazolidene hydrazines; triosephosphate isomerase; cruzipain; in vivo toxicity; zebrafish anti-T. cruzi and anti-Leishmania spp. activity; arylidene ketones; thiazolidene hydrazines; triosephosphate isomerase; cruzipain; in vivo toxicity; zebrafish
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MDPI and ACS Style

Álvarez, G.; Perdomo, C.; Coronel, C.; Aguilera, E.; Varela, J.; Aparicio, G.; Zolessi, F.R.; Cabrera, N.; Vega, C.; Rolón, M.; Rojas de Arias, A.; Pérez-Montfort, R.; Cerecetto, H.; González, M. Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.. Molecules 2017, 22, 709.

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