6533b82afe1ef96bd128c191
RESEARCH PRODUCT
Design, synthesis, and biological evaluation of thiophene analogues of chalcones.
Andrea BrancaleDelia PretiAntonella Di CristinaCarlota Lopez CaraTaradas SarkarRomeo RomagnoliManlio TolomeoOlga Cruz-lopezStefania GrimaudoMaria Dora CarrionErnest HamelPier Giovanni BaraldiNicola ZontaJan Balzarinisubject
G2 PhaseModels MolecularDouble bondStereochemistryClinical BiochemistryPharmaceutical ScienceEtherAntineoplastic Agentsmacromolecular substancesThiophenesBiochemistryChemical synthesischemistry.chemical_compoundMiceStructure-Activity RelationshipChalconesTubulinCell Line TumorDrug DiscoveryThiopheneMoietyAnimalsHumansMolecular BiologyCell Proliferationchemistry.chemical_classificationBinding SitesbiologyDose-Response Relationship DrugMolecular StructureArylOrganic ChemistryCell CycleBrainStereoisomerismTubulin ModulatorsTubulinchemistryDrug Designbiology.proteinMolecular MedicineCattleDrug Screening Assays AntitumorColchicineK562 CellsEnoneCell DivisionHeLa Cellsdescription
Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative activity and inhibition of tubulin assembly and colchicine binding to tubulin. The replacement of the double bond with a thiophene maintains antiproliferative activity and therefore must not significantly alter the relative conformation of the two aryl rings. The synthesized compounds were found to inhibit the growth of several cancer cell lines at nanomolar to low micromolar concentrations. In general, all compounds having significant antiproliferative activity inhibited tubulin polymerization with an IC(50)2microM. Several of these compounds caused K562 cells to arrest in the G2/M phase of the cell cycle.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-05-01 | Bioorganicmedicinal chemistry |