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Biological evaluation and structure-activity relationship of dithiocarbazate compounds and their metal complexes as trypanocidal agents

Grant number: 14/17754-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2015
Effective date (End): May 31, 2018
Field of knowledge:Health Sciences - Pharmacy
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Sérgio de Albuquerque
Grantee:Zumira Aparecida Carneiro
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


One hundred and five years after the discovery of Chagas disease, it is still a serious medical and social problem in Latin America due to its high morbidity. Chagas disease is caused by an intracellular protozoan, Trypanosoma cruzi (T. cruzi), and is a chronic and debilitating evolution. The limited number of drugs for this purpose has driven researchers to discover new drugs that can act in a more specific way and carrying low side effect. In this context the project proposed here aims to contribute. Based on the biological action of ditiocarbazatos, new molecules will be developed, as well as their complexes formed with iron, ruthenium and cobalt. The effect of the coordination of the metal will be evaluated for trypanocidal activity. The result will provide understand the effect of metal electron density in the ligand dithiocarbazate and understand about the site of interaction of the organic molecule with the parasite, given the fact that some of the sites inherent in this interaction will be linked to the metal ion. Antichagasic action will be evaluated by "screening" on the epimastigote forms of Tulahuen LacZ strain (T. cruzi) which will provide trypanocidal evaluation of prescription drugs. Biological testing in an aqueous medium and nanoparticle system will also be developed. In vitro results for the most active species will direct in vivo studies in which the assessment of parasitemia, survival, heart histology and qPCR analysis in the acute phase of the disease will be developed. Metabolism studies will provide understanding about the metabolites generated by drug administration. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARNEIRO, ZUMIRA A.; LIMA, JACKELINNE C.; LOPES, CARLA D.; GASPARI, ANA P. S.; DE ALBUQUERQUE, SERGIO; DINELLI, LUIS R.; VELOSO-SILVA, LAUDIMIR L. W.; PAGANELLI, MARCELLA O.; LIBARDI, SILVIA H.; OLIVEIRA, CAROLINA G.; et al. Heterobimetallic nickel(II) and palladium(II) complexes derived from S-benzyl-N- (ferrocenyl)methylenedithiocarbazate: Trypanocidal activity and interaction with Trypanosoma cruzi Old Yellow Enzyme (TcOYE). EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 180, p. 213-223, . (14/17754-0, 09/54011-8)

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