Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1

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The pentavalent antimonial therapy

Sharon Rose Aragão Macedo , Larissa Deadame de Figueiredo Nicolete , Amália dos Santos Ferreira , Neuza Biguinati de Barros , Roberto Nicolete ⁎ a Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil b Programa de Pós-Graduação em Biologia Experimental (PGBioexp), Universidade Federal de Rondônia, BR-364, Km 9...

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Leishmania TDR1 structure, a unique trimeric glutathione transferase capable of deglutathionylation and antimonial prodrug activation.

Thiol-dependent reductase I (TDR1), an enzyme found in parasitic Leishmania species and Trypanosoma cruzi, is implicated in deglutathionylation and activation of antimonial prodrugs used to treat leishmaniasis. The 2.3 Å resolution structure of TDR1 reveals a unique trimer of subunits each containing two glutathione-S-transferase (GST) domains. The similarities of individual domains and compari...

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Anti Leishmanial Activities of Some Antidepressant Drugs

Leishmaniasis is one of the most diverse and complex vector-borne metazoonosis diseases[1]. The causing agent is at least 17 species[2] of obligate intracellular protozoan parasites that belong to the genus Leishmania[3]. It is transmitted to human by the bite of phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia in the old and new worlds respectively[4]. The species are in ...

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Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru.

BACKGROUND Treatment for cutaneous leishmaniasis (CL) with standard pentavalent antimonial therapy is hampered by cumbersome administration, toxicity, and potential failure. Knowledge of factors influencing treatment outcome is essential for successful management. METHODS A case-control study of incident cases was performed with patients experiencing their first CL episode. The standard treat...

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Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs.

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobo...

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ژورنال

عنوان ژورنال: Biochemical Journal

سال: 2004

ISSN: 0264-6021,1470-8728

DOI: 10.1042/bj20040283