6533b854fe1ef96bd12aea5e
RESEARCH PRODUCT
Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues
Anna CarboneValentina DoldiMarzia PennatiAlessia LopergoloAlessandra MontalbanoVirginia SpanòPaola BarrajaNadia ZaffaroniGirolamo CirrincioneBarbara ParrinoStefania SbarraPatrizia Dianasubject
Cell cycle checkpointCDK1 InhibitorsAntiproliferative Activity CDK1 Inhibitors Diffuse Malignant Peritoneal Mesothelioma Nortopsentin Analogues SurvivinPyridinesStereochemistrySurvivinDiffuse Malignant Peritoneal MesotheliomaAntineoplastic AgentsApoptosisAntiproliferative Activity; CDK1 Inhibitors; Diffuse Malignant Peritoneal Mesothelioma; Nortopsentin Analogues; SurvivinBiochemistryCell LineAntiproliferative ActivityStructure-Activity Relationshipchemistry.chemical_compoundDrug DiscoverySurvivinHumansCytotoxic T cellProtein Kinase InhibitorsCell ProliferationPharmacologyCyclin-dependent kinase 1AlkaloidOrganic ChemistrySettore CHIM/08 - Chimica FarmaceuticaPaclitaxelchemistryCell cultureApoptosisNortopsentin AnaloguesMolecular Medicinedescription
A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G 2 /M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr 34 and to increase the cytotoxic activity of paclitaxel in STO cells.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |