title: Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Chemistry, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Brachwitz
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Voigt
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Christoph
authors.initials: C
authors.lastname: Schächtele
authors.forename: Josef
authors.initials: J
authors.lastname: Molnár
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D001372:Aza Compounds; D005449:Fluorenes; D007364:Intercalating Agents; D016203:CDC2 Protein Kinase