Search results for " CDK1"

showing 7 items of 7 documents

NUOVI DERIVATI PIRROLO[2,3-B]PIRIDINICI SOSTITUITI, PROCEDIMENTO PER LA LORO PREPARAZIONE E LORO IMPIEGO TERAPEUTICO.

2013

Analoghi della Nortopsentina Pirrolo[23-b]pirimidineSettore CHIM/08 - Chimica FarmaceuticaAttività antiproliferativa CDK1
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N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES

2009

A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by…

Models MolecularStereochemistryCyclin BPharmaceutical ScienceAntineoplastic AgentsCyclin BStructure-Activity RelationshipCDC2 Protein KinaseDrug DiscoveryHumansStructure–activity relationshipCell ProliferationCyclin-dependent kinase 1Binding SitesbiologyCell growthChemistryImidazolesN-(1H-indazolyl)benzamides 1H-indazole-3-carboxamides CDK1 Molecular dockingBiological activitySettore CHIM/08 - Chimica FarmaceuticaBiochemistryDocking (molecular)Cell cultureDrug DesignBenzamidesbiology.proteinDrug Screening Assays AntitumorK562 CellsCDC2 Protein KinaseProtein Binding
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Novel 1H‑Pyrrolo[2,3‑b]pyridine Derivative Nortopsentin Analogues: Synthesis and Antitumor Activity in Peritoneal Mesothelioma Experimental Models

2013

In this study, we describe the synthesis of new nortopsentin analogues, 1H-pyrrolo[2,3-b]pyridine derivatives and their biological effects in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rare and rapidly fatal disease, poorly responsive to conventional therapies. The three most active compounds, 1f (3-[2-(5-fluoro-1-methyl-1H-indol-3- yl)-1,3-thiazol-4-yl]-1H-pyrrolo[2,3-b]pyridine), 3f (3-[2-(1H-indol-3-yl)-1,3- thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b]pyridine), and 1l (3-[2-(5-fluoro-1- methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b] pyridine), which were shown to act as cyclin-dependent kinase 1 inhibitors, consistently reduced DMPM cell p…

CDK1 inhibitorsmalignant peritoneal mesothelioma3‑b]pyridineNortopsentin Analogues1H‑Pyrrolo[21H‑Pyrrolo[23‑b]pyridineCDK1 inhibitorsNortopsentin AnalogueSettore CHIM/08 - Chimica Farmaceuticamalignant peritoneal mesothelioma; 1H‑Pyrrolo[2; 3‑b]pyridine; Nortopsentin Analogues; CDK1 inhibitors
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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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A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells

2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4…

Indolespancreatic cancerPharmaceutical ScienceAntineoplastic AgentsApoptosisArticleAnalytical ChemistryStructure-Activity RelationshipQD241-441CDK1 inhibitorantiproliferativeCatalytic DomainCell Line TumorDrug DiscoveryCDC2 Protein KinaseHumansPhysical and Theoretical ChemistryProtein Kinase InhibitorsCell ProliferationOxadiazolesOrganic ChemistryImidazoles124-oxadiazolePDACmarine alkaloidMolecular Docking SimulationPancreatic NeoplasmsChemistry (miscellaneous)Molecular Medicinemarine alkaloidstopsentinDrug Screening Assays Antitumor124-oxadiazole; marine alkaloids; topsentin; CDK1 inhibitor; pancreatic cancer; PDAC; antiproliferative; apoptosisCarcinoma Pancreatic DuctalProtein BindingSignal TransductionMolecules
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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 nortopsenti…

2014

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 paclit…

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 Medicine
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Study of the combined effects of CDK1 inhibitors and senolytic drugs for the clearance of aneuploid-senescent cells

2022

Despite the progresses in discovering new therapeutic drugs and treatments, cancer is still one of the main causes of death. The biggest part of available treatments, moreover, is not always effective against tumour spread and it also has negative effects on the healthy tissues of the individual. For this reason, it is extremely relevant to find new strategies to avoid side effects during the anti-cancer therapies. Aneuploidy, an aberrant number of chromosomes in the cell, is a typical condition of cancer cells caused mainly by segregation errors and chromosomal instability (CIN). CIN is a process by which higher rate of chromosome segregation defects occurs by different mechanisms (chromos…

FlavonoidsSettore BIO/18 - GeneticaSettore BIO/10 - BiochimicaCDK1 inhibitionSenolyticCell cycleAneuploidySenescence: CDK1
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