PUBLICATION
Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp
- Authors
- 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.
- ID
- ZDB-PUB-170510-10
- Date
- 2017
- Source
- Molecules 22(5): (Journal)
- Registered Authors
- Aparicio, Gonzalo, Zolessi, Flavio
- Keywords
- anti-T. cruzi and anti-Leishmania spp. activity, arylidene ketones, cruzipain, in vivo toxicity, thiazolidene hydrazines, triosephosphate isomerase, zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Chagas Disease/drug therapy*
- Chagas Disease/metabolism
- Chagas Disease/pathology
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical
- Humans
- Hydrazines
- Ketones
- Leishmania braziliensis/growth & development*
- Leishmania infantum/growth & development*
- Leishmaniasis, Cutaneous/drug therapy*
- Leishmaniasis, Cutaneous/metabolism
- Leishmaniasis, Cutaneous/pathology
- Leishmaniasis, Visceral/diet therapy*
- Leishmaniasis, Visceral/metabolism
- Leishmaniasis, Visceral/pathology
- Mice
- Thiazolidines
- Trypanocidal Agents*/chemical synthesis
- Trypanocidal Agents*/chemistry
- Trypanocidal Agents*/pharmacology
- Trypanosoma cruzi/growth & development*
- Zebrafish
- PubMed
- 28481276 Full text @ Molecules
Citation
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. (2017) Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp. Molecules. 22(5).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping