Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties
Résumé
The first series of synthetic 1-aza-9-oxafluorenes with cytostatic activities in the micromolar range was evaluated as cyclin-dependent kinase (CDK1) inhibitors. Activity was found to be selective in comparison to the inhibition of other kinases within the CDK family. Compounds were shown to inhibit the membrane-efflux pump P-glycoprotein responsible for multidrug resistance in cancer cells. First structure-activity relationships are discussed.
Mots clés
Animals Antineoplastic Agents/*chemical synthesis/chemistry/pharmacology Aza Compounds/*chemical synthesis/chemistry/pharmacology CDC2 Protein Kinase/*antagonists & inhibitors Drug Resistance
Neoplasm Drug Screening Assays
Antitumor Fluorenes/*chemical synthesis/chemistry/pharmacology Intercalating Agents/*chemical synthesis/chemistry/pharmacology Mice P-Glycoproteins/*metabolism Research Support
Non-U.S. Gov't Structure-Activity Relationship Tumor Cells
Cultured