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SELECTIVE ESTROGEN RECEPTOR MODULATORS AS DRUG CANDIDATES FOR VISCERAL LEISHMANIASIS: EVALUATION OF DRUG COMBINATIONS AND INVESTIGATION OF LEISHMANICIDAL MECHANISMS OF ACTION

Grant number: 11/21970-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Silvia Reni Bortolin Uliana
Grantee:Juliana Quero Reimão Dalla Zanna
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmaniasis is endemic in 98 countries, with about 12 million people infected worldwide. Visceral leishmaniasis (VL), given its high incidence and mortality, is considered by the World Health Organization as one of the most important diseases nowadays. Leishmaniasis treatment relies on a limited therapeutic arsenal, with toxic drugs administered by the parenteral route such as pentavalent antimonials, amphotericin B and pentamidine. The toxicity, high cost and route of administration of these drugs, coupled with parasite resistance to antimonials in some regions, indicate that the discovery of new alternatives for leishmaniasis treatment is essential, as new drugs or new chemotherapy regimens using drug combinations. The leishmanicidal activity of tamoxifen was recently described in experimental models of leishmaniasis. Therefore, the aim of this project is to characterize the antileishmanial activity of the Selective Estrogen Receptor Modulators (SERMs) raloxifene and tamoxifen, alone or in combinations of drugs on LV models. For that purpose, a model of LV using luminescent parasites will be implemented. In parallel, this study focuses on understanding the leishmanicidal mechanism of action of these compounds. Through this project we are looking to identify new drug candidates or combination therapy schemes for VL treatment. We believe that data obtained in this project might provide the basis for a clinical trial design, given that tamoxifen and raloxifene have well established clinical safety profiles.

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.; 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: 10.
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.
REIMAO, JULIANA QUERO; MESQUITA, JULIANA TONINI; FERREIRA, DAIANE DIAS; TEMPONE, ANDRE GUSTAVO. Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism of Leishmania (L.) infantum. Evidence-based Complementary and Alternative Medicine, 2016. Web of Science Citations: 1.
REIMAO, JULIANA Q.; OLIVEIRA, JORDANA C.; TRINCONI, CRISTIANA T.; COTRIM, PAULO C.; COELHO, ADRIANO C.; ULIANA, SILVIA R. B. Generation of Luciferase-Expressing Leishmania infantum chagasi and Assessment of Miltefosine Efficacy in Infected Hamsters through Bioimaging. PLoS Neglected Tropical Diseases, v. 9, n. 2 FEB 2015. Web of Science Citations: 11.
REIMAO, JULIANA Q.; MIGUEL, DANILO C.; TANIWAKI, NOEMI N.; TRINCONI, CRISTIANA T.; YOKOYAMA-YASUNAKA, JENICER K. U.; ULIANA, SILVIA R. B. Antileishmanial Activity of the Estrogen Receptor Modulator Raloxifene. PLoS Neglected Tropical Diseases, v. 8, n. 5 MAY 2014. Web of Science Citations: 13.
MESQUITA, JULIANA T.; TEMPONE, ANDRE G.; REIMAO, JULIANA Q. Combination therapy with nitazoxanide and amphotericin B, Glucantime (R), miltefosine and sitamaquine against Leishmania (Leishmania) infantum intracellular amastigotes. Acta Tropica, v. 130, p. 112-116, FEB 2014. Web of Science Citations: 9.
REIMAO, JULIANA Q.; TRINCONI, CRISTIANA T.; YOKOYAMA-YASUNAKA, JENICER K.; MIGUEL, DANILO C.; KALIL, SANDRA P.; ULIANA, SILVIA R. B. Parasite burden in Leishmania (Leishmania) amazonensis-infected mice: Validation of luciferase as a quantitative tool. Journal of Microbiological Methods, v. 93, n. 2, p. 95-101, MAY 2013. Web of Science Citations: 23.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.