Peptidomimetic nitrile inhibitors of malarial protease falcipain-2 with high selectivity against human cathepsins.
Bioorg Med Chem Lett
; 28(9): 1540-1544, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29615344
ABSTRACT
Falcipain-2 (FP2) is an essential enzyme in the lifecycle of malaria parasites such as Plasmodium falciparum, and its inhibition is viewed as an attractive mechanism of action for new anti-malarial agents. Selective inhibition of FP2 with respect to a family of human cysteine proteases (that include cathepsins B, K, L and S) is likely to be required for the development of agents targeting FP2. Here we describe a series of P2-modified aminonitrile based inhibitors of FP2 that provide a clear strategy toward addressing selectivity for the P. falciparum and show that it can provide potent FP2 inhibitors with strong selectivity against all four of these human cathepsin isoforms.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Cisteína Endopeptidases
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Catepsinas
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Inibidores de Cisteína Proteinase
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Peptidomiméticos
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Antimaláricos
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Nitrilas
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article