6533b7d3fe1ef96bd125fff6

RESEARCH PRODUCT

Synthesis and Biological Evaluation of 1-Methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a New Class of Antimitotic Agents and Tubulin Inhibitors

Hsing Pang HsiehTaradas SarkarNicola ZontaPier Giovanni BaraldiStefania GrimaudoRomeo RomagnoliMojgan Aghazadeh TabriziManlio TolomeoAndrea BrancaleJan BalzariniCarlota Lopez CaraMaria Dora CarrionOlga Cruz-lopezErnest HamelDelia PretiAntonella Di Cristina

subject

Models MolecularIndolesStereochemistryAlkylationAntimitotic AgentsChemical synthesisMiceStructure-Activity RelationshipBiopolymersTubulinCell Line TumorDrug DiscoveryStructure–activity relationshipAnimalsHumansIndole testBinding SitesbiologyTubulin ModulatorsChemistryBiological activityTubulin ModulatorsTubulinbiology.proteinMolecular MedicineAntimitotic AgentDrug Screening Assays AntitumorColchicineProtein Binding

description

The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.

yearjournalcountryeditionlanguage
2008-02-09
10.1021/jm7011547http://hdl.handle.net/10447/34018