Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties.
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.
Brachwitz
Kristin
K
Institute of Pharmaceutical Chemistry, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany.
Voigt
Burkhardt
B
Meijer
Laurent
L
Lozach
Olivier
O
Schächtele
Christoph
C
Molnár
Josef
J
Hilgeroth
Andreas
A
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
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D001372:Aza Compounds; D005449:Fluorenes; D007364:Intercalating Agents; D016203:CDC2 Protein Kinase