Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase-dihydrofolate reductase.
Bioorg Med Chem Lett
; 24(4): 1232-5, 2014 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-24440298
ABSTRACT
The parasite Toxoplasma gondii can lead to toxoplasmosis in those who are immunocompromised. To combat the infection, the enzyme responsible for nucleotide synthesis thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a suitable drug target. We have used virtual screening to determine novel allosteric inhibitors at the interface between the two TS domains. Selected compounds from virtual screening inhibited TS activity. Thus, these results show that allosteric inhibition by small drug-like molecules can occur in T. gondii TS-DHFR and pave the way for new and potent species-specific inhibitors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timidilato Sintase
/
Toxoplasma
/
Avaliação Pré-Clínica de Medicamentos
/
Inibidores Enzimáticos
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Complexos Multienzimáticos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos