6533b85bfe1ef96bd12baa2c
RESEARCH PRODUCT
Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands
Giulia VignaroliStephan A. OhnmachtMekala GunaratnamStephen NeidleCristina Cianciminosubject
Phenotypic screeningClinical BiochemistryPharmaceutical ScienceG-quadruplexLigandsBiochemistrychemistry.chemical_compoundInhibitory Concentration 50Structure-Activity RelationshipHeterocyclic CompoundsCell Line TumorDrug DiscoveryHumansMolecular BiologyGeneCell ProliferationOrganic ChemistryCombinatorial chemistrySmall moleculeSettore CHIM/08 - Chimica FarmaceuticaG-QuadruplexeschemistryMolecular MedicineHuman genomeQuadruplex Anti-proliferative Phenotypic screening Telomerase OxazolesDrug Screening Assays AntitumorLead compoundDerivative (chemistry)DNAdescription
Abstract Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure–activity relationships of the series are not obviously related to the quadruplex binding.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-10-01 |