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From trypanosomes to Leishmania: novel drug candidates for the treatment of neglected parasitic diseases

Grant number: 11/50577-7
Support type:Regular Research Grants
Duration: July 01, 2011 - June 30, 2013
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Cooperation agreement: King's College London
Principal Investigator:André Gustavo Tempone Cardoso
Grantee:André Gustavo Tempone Cardoso
Principal investigator abroad: Gerd Wagner
Institution abroad: King's College London, England
Home Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:08/09260-7 - Therapeutic combinations for visceral leishmaniasis: the antileishmanial potential of calcium channel blockers and the use of liposomal nanoformulations, AP.R


Visceral Leishmaniasis (VL) is a parasitic tropical disease, resulting in a progressive and fatal infection. The increase in the number of cases in non-endemic areas and the high toxicity of the chemotherapy demonstrate the urgent necessity of novel drugs. Establishing collaboration between the Kings College London and Instituto Adolfo Lutz would create considerable synergies for the both research groups. The current FAPESP project (2008/09260-7) coordinated by Prof. Tempone would benefit directly from the collaboration with Dr. Wagner’s group. As a part of our current project, the in vitro screening of molecules is an important phase for the selection of new lead candidates against Leishmania. The lack of a higher number of synthetic compounds to be screened, limits the time-consuming drug discovery process. As a consequence, parasitologists must call upon clinically available drugs for drug discovery studies, with a limited arsenal of commercially available compounds (mainly Sigma-Aldrich). The interaction of the Tempone laboratory with an experienced medicinal chemistry group would therefore improve our search for a lead compound in this initial phase, since Dr. Wagner would provide small molecule libraries to be tested in our in vitro models. Furthermore, the information of structure-activity relationships against Leishmania, could provide valuable data for the design of novel inhibitors with low mammalian toxicity and higher anti-leishmanial activity. In addition, we will also provide the in vitro screening in our available. Trypanosoma cruzi model. The Wagner group will provide unique compound libraries to the Tempone group for screening against T. cruzi and Leishmania sp. in existing bioassays in the Tempone laboratory. These human parasites, the causative agents of, respectively, Chagas disease and Leishmaniasis are closely related to T. brucei. It is therefore highly likely that inhibitors of T. brucei may also be active against these parasites, and the collaboration with Prof. Tempone will allow us to this exciting possibility. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Collaborative research augments therapy for visceral leishmaniasis 
Scientists treat visceral leishmaniasis with an adapted drug 

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)
GEHRKE, SEBASTIAN S.; PINTO, ERIKA G.; STEVERDING, DIETMAR; PLEBAN, KARIN; TEMPONE, ANDRE G.; HIDER, ROBERT C.; WAGNER, GERD K. Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators. Bioorganic & Medicinal Chemistry, v. 21, n. 3, p. 805-813, FEB 1 2013. Web of Science Citations: 12.

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