Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23427

Type
Article
Copyright
Restricted access
Embargo date
2030-01-01
Collections
Share

Statistics
Metadata
Show full item record

THE POTENT CELL PERMEABLE CALPAIN INHIBITOR MDL28170 AFFECTS THE INTERACTION OF LEISHMANIA AMAZONENSIS WITH MACROPHAGES AND SHOWS ANTI-AMASTIGOTE ACTIVITY
Marinho, Fernanda A. et al. | Date Issued: 2017
Author
Marinho, Fernanda A.
Sangenito, Leandro S.
Oliveira, Simone S. C.
Arruda, Luciana B. de
d`Avila-Levy, Claudia M.
Santos, André L. S.
Branquinha, Marta H.
Affilliation
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Laboratório de Gene[tica e Imunologia das Infecções Virais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Coleção de Protozoários. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil.
Abstract
Since the discovery of the28 first drugs used in leishmaniasis treatment up to now, the search for compounds with anti-Leishmania activity without toxic effects and able to overcome the emergency of resistant strains remains a major goal to combat this neglected disease. With this in mind, in the present work, we evaluated the effects of the calpain inhibitor MDL28170 on the interaction process of Leishmania amazonensis promastigote forms with murine peritoneal macrophages and on the intracellular amastigotes. Our results showed that the calpain inhibitor MDL28170 at 15 and 30μM significantly reduced the interaction process of promastigotes with macrophages by 16% and 41%, respectively. The inhibitor was also able to drastically reduce the number of infected macrophages in a time- and dose-dependent manner: after only 24h, MDL28170 was able to significantly diminish the infection rate, presenting an IC50 value of 18.2μM for amastigotes. The treatment with MDL28170 did not alter the nitric oxide production, but the production of TNF-α was significantly raised. Altogether, the results presented here contribute to the search of new proteolytic inhibitors able to act in a selective and effective manner against the diseases caused by trypanosomatids.
Keywords in Portuguese
Leishmaniose
Leishmania amazonensis
Inibidor de calpaína
Processo de interação
Amastigotas intracelulares
 
Keywords
Leishmaniasis
Leishmania amazonensis
Calpain inhibitor
Interaction process
Intracellular amastigotes
 
Publisher
Elsevier
Citation
MARINHO, Fernanda A. et al. The potent cell permeable calpain inhibitor MDL28170 affects the interaction of Leishmania amazonensis with macrophages and shows antiamastigote activity. Parasitology International, v.66, p.579-583, June 2017.
DOI
10.1016/j.parint.2017.06.010
ISSN
1383-5769