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

• Processo: 11/50577-7
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Vigência: 01 de julho de 2011 - 30 de junho de 2013
• Área do conhecimento: Ciências Biológicas - Parasitologia - Protozoologia de Parasitos
• Convênio/Acordo: King's College London
• Pesquisador responsável: André Gustavo Tempone Cardoso
• Beneficiário: André Gustavo Tempone Cardoso
• Pesq. responsável no exterior: Gerd Wagner
• Instituição no exterior: King's College London, Inglaterra
• Instituição Sede: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brasil
• Vinculado ao auxílio: 08/09260-7 - Combinações terapêuticas na leishmaniose visceral: o potencial anti-leishmania de bloqueadores de canais de cálcio e o uso de nanoformulações lipossomais, AP.R
• Assunto(s): Química médica Antiparasitários Leishmania Leishmaniose Trypanosoma cruzi Doença de Chagas
• Palavra(s)-Chave do Pesquisador: Doenca De Chagas | Leishmania | Leishmaniose | Quimica Medicinal | Terapia | Trypanosoma Cruzi

Resumo

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)

Publicações científicas

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

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. (11/50577-7)