6533b872fe1ef96bd12d399d
RESEARCH PRODUCT
3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity
Patrizia DianaGloria Di VitaGirolamo CirrincioneM. A. LivreaAnna CarboneCristina CianciminoLuisa TesorierePaola BarrajaAlessandro AttanzioVirginia SpanòBarbara ParrinoAlessandra Montalbanosubject
IndolesHalogenationPyridines3-b]pyridinesPharmaceutical ScienceApoptosisAntiproliferative activity3-[4-(1<i>H</i>-indol-3-yl)-13-thiazol-2-yl]-1<i>H</i>-pyrrolo[23-<i>b</i>]pyridineschemistry.chemical_compoundNeoplasmsDrug DiscoveryImidazoleMoietyindolyl alkaloidsPharmacology Toxicology and Pharmaceutics (miscellaneous)lcsh:QH301-705.5Membrane Potential MitochondrialMolecular Structure3-[4-(1H-indol-3-yl)-1; 3-thiazol-2-yl]-1H-pyrrolo[2; 3-b]pyridines; Antiproliferative activity; Indolyl alkaloids; Marine alkaloids; Nortopsentin analogues; Drug Discovery3003 Pharmaceutical ScienceImidazolesPhosphatidylserineMitochondrianortopsentin analoguesIndolyl alkaloidmarine alkaloidsG2 PhaseStereochemistryNortopsentin analogueAntineoplastic AgentsMethylationResting Phase Cell CycleArticleAlkaloids3-[4-(1H-indol-3-yl)-1Cell Line TumorHumansPyrroles3-[4-(1H-indol-3-yl)-13-thiazol-2-yl]-1H-pyrrolo[23-b]pyridines3-thiazol-2-yl]-1H-pyrrolo[2ThiazoleCell ProliferationIndole testNatural productCell growthDrug Discovery3003 Pharmaceutical ScienceSettore CHIM/08 - Chimica FarmaceuticaThiazoleschemistrylcsh:Biology (General)Cell cultureDrug DesignMarine alkaloid3-[4-(1H-indol-3-yl)-13-thiazol-2-yl]-1H-pyrrolo[23-b]pyridinedescription
A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-04-03 |