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Evaluation of candidate drugs for the treatment of Leishmaniasis in Brazil

Grant number: 15/09080-2
Support type:Regular Research Grants
Duration: August 01, 2015 - January 31, 2018
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Silvia Reni Bortolin Uliana
Grantee:Silvia Reni Bortolin Uliana
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Adriano Cappellazzo Coelho ; Edgar Marcelino de Carvalho Filho ; Juliana Quero Reimão Dalla Zanna ; Paulo Roberto Lima Machado

Abstract

The various clinical forms of leishmaniasis are highly prevalent diseases in Brazil. In recent years, the classical, predominantly rural, geographical distribution of the disease has changed and we have witnessed a considerable increase in the number of urban cases. Only a few drugs are available for leishmaniasis treatment and these display several disadvantages such as high cost and toxicity, parenteral use and, in some instances, low efficacy due to selection of resistant parasites. The repositioning to leishmaniasis chemotherapy of two antineoplasic drugs, miltefosine and tamoxifen, has been proposed in the last few years. Miltefosine has already been approved for clinical use in some countries and tamoxifen has been shown to be effective in pre-clinical settings. This proposal is focused at contributing for the identification and/or validation of new alternatives for leishmaniasis chemotherapy. Specific aims are: (1) to evaluate the efficacy of the association of tamoxifen and meglumine antimoniate in a phase II pilot clinical test in localized cutaneous leishmaniasis patients; (2) investigate the leishmanicidal mechanisms of action of tamoxifen against Leishmania; (3) determine the antileishmanial activity of synthetic compounds structurally related to previously studied selective modulators of the estrogen receptor and (4) to contribute in the evaluation of the potential efficacy of miltefosine in Brazil - this is to be accomplished through determining the susceptibility of Brazilian Leishmania isolates to miltefosine and studying the molecular basis of differences in susceptibility. (AU)

Scientific publications (7)
(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)
TRINCONI, CRISTIANA T.; MIGUEL, DANILO C.; SILBER, ARIEL M.; BROWN, CHRISTOPHER; MINA, JOHN G. M.; DENNY, PAUL W.; HEISE, NORTON; ULIANA, SILVIA R. B. Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, v. 8, n. 3, p. 475-487, DEC 2018. Web of Science Citations: 1.
ESPADA, CAROLINE R.; ORTIZ, PAOLA A.; SHAW, JEFFREY J.; BARRAL, ALDINA M. P.; COSTA, JACKSON M. L.; ULIANA, SILVIA R. B.; COELHO, ADRIANO C. Identification of Leishmania (Viannia) species and clinical isolates of Leishmania (Leishmania) amazonensis from Brazil using PCR-RFLP of the heat-shock protein 70 gene reveals some unexpected observations. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 91, n. 4, p. 312-318, AUG 2018. Web of Science Citations: 5.
TRINCONI, CRISTIANA T.; REIMAO, JULIANA Q.; BONANO, I, VIVIAN; ESPADA, CAROLINE R.; MIGUEL, DANILO C.; YOKOYAMA-YASUNAKA, JENICER K. U.; ULIANA, SILVIA R. B. Topical tamoxifen in the therapy of cutaneous leishmaniasis. Parasitology, v. 145, n. 4, SI, p. 490-496, APR 2018. Web of Science Citations: 7.
ULIANA, SILVIA R. B.; TRINCONI, CRISTIANA T.; COELHO, ADRIANO C. Chemotherapy of leishmaniasis: present challenges. Parasitology, v. 145, n. 4, SI, p. 464-480, APR 2018. Web of Science Citations: 27.
ESPADA, CAROLINE R.; RIBEIRO-DIAS, FATIMA; DORTA, MIRIAM L.; DE ARAUJO PEREIRA, LEDICE INACIA; DE CARVALHO, EDGAR M.; MACHADO, PAULO R.; SCHRIEFER, ALBERT; YOKOYAMA-YASUNAKA, JENICER K. U.; COELHO, ADRIANO C.; ULIANA, SILVIA R. B. Susceptibility to Miltefosine in Brazilian Clinical Isolates of Leishmania (Viannia) braziliensis. American Journal of Tropical Medicine and Hygiene, v. 96, n. 3, p. 656-659, 2017. Web of Science Citations: 2.
COELHO, ADRIANO C.; OLIVEIRA, JORDANA C.; ESPADA, CAROLINE R.; REIMAO, JULIANA Q.; TRINCONI, CRISTIANA T.; ULIANA, SILVIA R. B. A Luciferase-Expressing Leishmania braziliensis Line That Leads to Sustained Skin Lesions in BALB/c Mice and Allows Monitoring of Miltefosine Treatment Outcome. PLoS Neglected Tropical Diseases, v. 10, n. 5 MAY 2016. Web of Science Citations: 4.
TRINCONI, CRISTIANA T.; REIMAO, JULIANA Q.; COELHO, ADRIANO C.; ULIANA, SILVIA R. B. Efficacy of tamoxifen and miltefosine combined therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis. Journal of Antimicrobial Chemotherapy, v. 71, n. 5, p. 1314-1322, MAY 2016. Web of Science Citations: 14.

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