Search results for "3-b]pyridines"

showing 3 items of 3 documents

Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogu…

2015

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contr…

G2 Phaseantiproliferative activitybis-indolyl alkaloidsStereochemistryPyridinesPharmaceutical ScienceNortopsentin analoguesthiazolyl-bis-pyrrolo [23-b]pyridinesVacuoleArticlechemistry.chemical_compoundDrug DiscoveryImidazoleHumansPyrrolesautophagic deathThiazolelcsh:QH301-705.5Pharmacology Toxicology and Pharmaceutics (miscellaneous)Cell ProliferationIndole testMembrane Potential MitochondrialnortopsentinsDose-Response Relationship DrugMolecular Structureindolyl-thiazolyl-pyrrolo[23-c]pyridinesthiazolyl-bis-pyrrolo[23-b]pyridinesapoptosisPhosphatidylserineCell cycleHCT116 CellsSettore CHIM/08 - Chimica Farmaceuticaindolyl-thiazolyl-pyrrolo[23-<i>c</i>]pyridinesThiazoleslcsh:Biology (General)chemistryCytoplasmApoptosismarine alkaloidsthiazolyl-bis-pyrrolo [23-<i>b</i>]pyridinesMarine drugs
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Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues

2017

A new series of thiazole nortopsentin analogues was conveniently synthesized with fair overall yields. The antiproliferative activity of the new derivatives was tested against different human tumor cell lines of the NCI full panel. Four of them showed good antitumor activity with GI(50) values from micro to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and DNA fragmentation. The most active and selective of the new thiazoles confined viable cells in G2/M phase and markedly inhibited in vitro CDK1 activity. (C) 2017 Elsevier Masson SAS.

0301 basic medicineIndolesCell SurvivalStereochemistryMolecular ConformationNortopsentin analogues3-b]pyridinesAntineoplastic AgentsApoptosisMarine alkaloids Nortopsentin analogues Antiproliferative activity Apoptosis CDK1 inhibitors Thiazolyl-1H-pyrrolo[23-b]pyridinesAntiproliferative activity01 natural sciencesStructure-Activity Relationship03 medical and health scienceschemistry.chemical_compoundMarine alkaloidsCDC2 Protein KinaseDrug DiscoveryHumansThiazoleProtein Kinase InhibitorsCell ProliferationPharmacologyCyclin-dependent kinase 1Dose-Response Relationship DrugMarine alkaloids; Nortopsentin analogues; Antiproliferative activity; Apoptosis; CDK1 inhibitors; Thiazolyl-1H-pyrrolo[2; 3-b]pyridines010405 organic chemistryOrganic ChemistryImidazolesGeneral MedicinePhosphatidylserineThiazolyl-1H-pyrrolo[2Settore CHIM/08 - Chimica FarmaceuticaCyclin-Dependent KinasesIn vitro0104 chemical sciencesCDK1 inhibitors030104 developmental biologyMembranechemistryCell cultureApoptosisMCF-7 CellsDNA fragmentationCaco-2 CellsDrug Screening Assays Antitumor
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3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity

2015

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 dysfunctio…

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]pyridine
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