title: Antileishmanial activity of MDL 28170, a potent calpain inhibitor.
abstract: 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.
authors.affiliation: 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
authors.forename: Claudia M
authors.initials: CM
authors.lastname: d'Avila-Levy
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Marinho
authors.forename: Lívia O
authors.initials: LO
authors.lastname: Santos
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Martins
authors.forename: André L S
authors.initials: AL
authors.lastname: Santos
authors.forename: Marta H
authors.initials: MH
authors.lastname: Branquinha
mesh_terms: 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
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D006023:Glycoproteins; C039304:calpain inhibitors; D002154:Calpain; C058076:calpain inhibitor III