In-vitro antileishmanial potential of peptide drug hirudin.
Chem Biol Drug Des
; 89(1): 67-73, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27483399
ABSTRACT
Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin (GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC50 values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC50 values of 0.60 ± 0.36 µg/mL and 0.43 ± 0.23 µg/mL, respectively, in a dose- and time-dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD50 value of 860.11 ± 53.44 µg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hirudinas
/
Leishmania
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Drug Des
Ano de publicação:
2017
Tipo de documento:
Article