Combined Scaffold Evaluation and Systems-Level Transcriptome-Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes.
ChemMedChem
; 14(18): 1653-1661, 2019 09 18.
Article
em En
| MEDLINE
| ID: mdl-31140738
ABSTRACT
With evolutionary drug resistance impacting efforts to treat disease, the need for small molecules that exhibit novel molecular mechanisms of action is paramount. In this study, we combined scaffold-directed synthesis with a hybrid experimental and transcriptome analysis to identify bis-spirooxindole cyclopropanes that inhibit cancer cell proliferation through disruption of ribosomal function. These findings demonstrate the value of an integrated, biologically inspired synthesis and assay strategy for the accelerated identification of first-in-class cancer therapeutic candidates.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ribossomos
/
Compostos de Espiro
/
RNA Neoplásico
/
Ciclopropanos
/
Oxindóis
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article