Search results for " tubulin polymerization inhibitors"

showing 2 items of 2 documents

Pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles, a New Class of Antimitotic Agents Active against Multiple Malignant Cell Types

2020

A new class of pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles was synthesized for the treatment of hyperproliferative pathologies, including neoplasms. The new compounds were screened in the 60 human cancer cell lines of the NCI drug screen and showed potent activity with GI50 values reaching the nanomolar level, with mean graph midpoints of 0.08-0.41 μM. All compounds were further tested on six lymphoma cell lines, and eight showed potent growth inhibitory effects with IC50 values lower than 500 nM. Mechanism of action studies showed the ability of the new [1,2]oxazoles to arrest cells in the G2/M phase in a concentration dependent manner and to induce apoptosis through the mitochondrial…

CellsMitosisAntineoplastic AgentsApoptosisAntimitotic AgentsDrug Screening Assays[12]oxazoles antimitotic agents lymphoma tubulin polymerization inhibitorsDose-Response RelationshipStructure-Activity Relationshipchemistry.chemical_compoundModelsDrug DiscoverymedicineHumansStructure–activity relationshipColchicineOxazolesAntimitotic Agents; Antineoplastic Agents; Apoptosis; Cell Proliferation; Cells Cultured; Dose-Response Relationship Drug; Drug Screening Assays Antitumor; G2 Phase Cell Cycle Checkpoints; HeLa Cells; Humans; Mitosis; Models Molecular; Molecular Structure; Oxazoles; Structure-Activity RelationshipCell Proliferationchemistry.chemical_classificationReactive oxygen speciesCulturedMolecular StructureChemistryMolecularDepolarizationAntitumorMolecular biologyG2 Phase Cell Cycle CheckpointsMechanism of actionApoptosisCell cultureMolecular MedicineAntimitotic AgentDrugmedicine.symptomHeLa Cells
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Insight on [1,3]thiazolo[4,5-e]isoindoles as tubulin polymerization inhibitors

2021

A series of [1,3]thiazolo[4,5-e]isoindoles has been synthesized through a versatile and high yielding multistep sequence. Evaluation of the antiproliferative activity of the new compounds on the full NCI human tumor cell line panel highlighted several compounds that are able to inhibit tumor cell proliferation at micromolar-submicromolar concentrations. The most active derivative 11g was found to cause cell cycle arrest at the G2/M phase and induce apoptosis in HeLa cells, following the mitochondrial pathway, making it a lead compound for the discovery of new antimitotic drugs.

Models MolecularCell cycle checkpointIsoindoles1ApoptosisIsoindoles01 natural sciencesPolymerizationTubulin Polymerization InhibitorsCell cycle arrestHeLaStructure-Activity Relationship03 medical and health scienceschemistry.chemical_compoundTubulinDrug DiscoveryHumansTubulin polymerization inhibitors030304 developmental biologyPharmacology0303 health sciencesDose-Response Relationship DrugMolecular Structurebiology010405 organic chemistry3]thiazolo[4Organic ChemistryGeneral Medicinebiology.organism_classificationTubulin Modulators0104 chemical sciencesBiochemistrychemistryCell cultureApoptosis5-e]isoindoles13]thiazolo[45-e]isoindoles13]thiazolo[45-e]isoindoles; Apoptosis; Cell cycle arrest; Tubulin polymerization inhibitorsLead compoundDerivative (chemistry)HeLa CellsEuropean Journal of Medicinal Chemistry
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