6533b7dbfe1ef96bd12715a2
RESEARCH PRODUCT
N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES
Salvatore PlesciaMaria Grazia CusimanoGiuseppe DaidoneDomenico SchillaciClaudia ColombaStella CascioferroDemetrio RaffaLucina TitoneBenedetta MaggioManlio TolomeoMaria Valeria Raimondisubject
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 Bindingdescription
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 the above-mentioned compounds.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-01-01 |