Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase.
Bioorg Med Chem Lett
; 23(7): 2035-43, 2013 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-23453069
Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxoplasma
/
Triclosan
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Desenho de Fármacos
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Enoil-(Proteína de Transporte de Acila) Redutase (NADH)
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article