Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients

dc.creatorSantos, Lívia O.
dc.creatorVitório, Bianca S.
dc.creatorBranquinha, Marta H.
dc.creatorSilva, Conceição M. Pedroso e
dc.creatorSantos, André L. S.
dc.creatorLevy, Cláudia M. d`Avila
dc.date2015-08-19T13:49:30Z
dc.date2015-08-19T13:49:30Z
dc.date2013
dc.date.accessioned2023-09-26T23:13:53Z
dc.date.available2023-09-26T23:13:53Z
dc.identifierSANTOs, Lívia O.; et al. Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients. J Antimicrob Chemother, v.68, p.348–353, 2013.
dc.identifier1460-2091
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11545
dc.identifier10.1093/jac/dks410
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8888289
dc.descriptionObjectives: There is a general lack of effective and non-toxic chemotherapeutic agents for leishmaniasis and there is as yet no study about the effect of HIV peptidase inhibitors (HIV PIs) on Leishmania/HIV-coinfected patients. In the present work, we performed a comparative analysis of the spectrum of action of HIV PIs on different Leishmania spp., including strains obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. Methods: The effects of nelfinavir and saquinavir on Leishmania proliferation were assessed by means of a colorimetric assay (MTT). Subsequently, the effect of nelfinavir on aspartic peptidase activity from Leishmania spp. was assessed by following the degradation of the fluorogenic substrate MCA-G-K-P-I-L-F-F-R-L-K-DNP-Arg-NH2. Results: Nelfinavir was capable of significantly reducing the multiplication of many Leishmania reference strains and isolates obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. Leishmania major growth was inhibited by 50%, while all other flagellates were strongly inhibited (at least 94%), except for a Leishmania chagasi strain obtained from an HIV-positive patient under treatment with highly active antiretroviral therapy (HAART). Culture of this isolate in the presence of nelfinavir induced a considerable reduction in the aspartic peptidase activity. In addition, nelfinavir was also capable of inhibiting the aspartic peptidase activity of all Leishmania strains tested. Conclusions: The present data contribute to the study of the effect of HIV PIs on Leishmania infection and add new insights into the possibility of exploiting aspartic peptidases as promising targets in order to generate novel medications to treat leishmaniasis.
dc.formatapplication/pdf
dc.languageeng
dc.publisherOxford University Press
dc.rightsrestricted access
dc.subjectAspartyl peptidases
dc.subjectLeishmania/HIV coinfection
dc.subjectHIV peptidase inhibitors
dc.subjectchemotherapy
dc.subjectLeishmaniasis
dc.subjectProteases
dc.subjectLeishmaniose
dc.subjectQuimioterapia
dc.subjectProteases
dc.subjectNelfinavir
dc.subjectHIV
dc.subjectInibidores de Proteases
dc.titleNelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients
dc.typeArticle


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