6533b861fe1ef96bd12c57f7

RESEARCH PRODUCT

Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.

Jan BalzariniFrancesca FruttaroloDelia PretiJohn A. HadfieldMojgan Aghazadeh TabriziAnd Andrea BrancaleErnest HamelMaria Giovanna PavaniPier Giovanni BaraldiCarlota Lopez CaraStefania GrimaudoManlio TolomeoMaria Dora CarrionRomeo RomagnoliAntonella Di Cristina

subject

StereochemistryAntimitotic Agents/chemistry Antimitotic Agents/pharmacologymacromolecular substancesThiophenesAntimitotic AgentsChemical synthesischemistry.chemical_compoundMiceRadioligand AssayStructure-Activity RelationshipTubulinCell Line TumorDrug DiscoveryThiopheneStructure–activity relationshipAnimalsHumansCytotoxicityCell ProliferationBinding SitesbiologyBicyclic moleculeChemistryTubulin ModulatorsCell CycleTubulin ModulatorsTubulinbiology.proteinMolecular MedicineAntimitotic AgentDrug Screening Assays AntitumorColchicineProtein Binding

description

Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.

yearjournalcountryeditionlanguage
2007-01-01Journal of medicinal chemistry
10.1021/jm070050fhttps://pubmed.ncbi.nlm.nih.gov/17419607