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.
Original language | English (US) |
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Pages (from-to) | 1653-1661 |
Number of pages | 9 |
Journal | ChemMedChem |
Volume | 14 |
Issue number | 18 |
DOIs | |
State | Published - Sep 18 2019 |
Externally published | Yes |
Keywords
- drug discovery
- mechanism of action
- natural products
- spirooxindoles
- transcriptome network
ASJC Scopus subject areas
- Drug Discovery
- General Pharmacology, Toxicology and Pharmaceutics
- Molecular Medicine
- Biochemistry
- Pharmacology
- Organic Chemistry