Antileishmanial activity of MDL 28170, a potent calpain inhibitor.
Several calpain inhibitors are under development and some are useful agents against important human pathogens. We therefore investigated the effect of MDL 28170, a potent calpain inhibitor, on the growth of Leishmania amazonensis. After 48 h of treatment, the inhibitor exhibited a dose-dependent antileishmanial activity, with a 50% lethal dose (LD(50)) of 23.3 microM. The inhibitor promoted cellular alterations, such as the parasites becoming short and round. A calpain-like protein migrating at 80 kDa was identified by Western blotting. In addition, the calpain-like molecules were identified on the cell surface of the flagellate. These results add new in vitro insights into the exploitation of calpain inhibitors in treating parasitic infections and add this family of peptidases to the list of potential targets for development of more potent and specific inhibitors against trypanosomatids.
d'Avila-Levy
Claudia M
CM
Departamento de Microbiologia Geral, Instituto de Microbiologia Prof. Paulo de Góes (IMPPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil. masini@micro.ufrj.br
Marinho
Fernanda A
FA
Santos
Lívia O
LO
Martins
Juliana L
JL
Santos
André L S
AL
Branquinha
Marta H
MH
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D008856:Microscopy, Fluorescence; D021261:Parasitic Sensitivity Tests
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D006023:Glycoproteins; C039304:calpain inhibitors; D002154:Calpain; C058076:calpain inhibitor III