Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light.
J Enzyme Inhib Med Chem
; 31(sup3): 25-32, 2016.
Article
em En
| MEDLINE
| ID: mdl-27362889
ABSTRACT
Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2-b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI-FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinonas
/
Fosfatases cdc25
/
Avaliação Pré-Clínica de Medicamentos
/
Inibidores Enzimáticos
/
Indenos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França