Animals; Aza Compounds/chemical synthesis/chemistry/pharmacology; Carbazoles/chemical synthesis/chemistry/pharmacology; Carbohydrates/chemistry; Cell Line, Tumor; Cell Proliferation/drug effects; DNA/metabolism; DNA Topoisomerases, Type I/metabolism; Enzyme Inhibitors/chemical synthesis/chemistry/pharmacology; Humans; Indoles/chemical synthesis/chemistry/pharmacology; Mice; Molecular Structure; Nitrogen/chemistry; Protein Kinases/metabolism; Pyridines/chemistry; Structure-Activity Relationship; Topoisomerase I Inhibitors
Abstract :
[en] The synthesis of a new family of 7-aza-rebeccamycin analogues in which the sugar moiety is attached to the nitrogen of the pyridine ring is described. The capacity of the newly synthesized compounds to bind to DNA and to inhibit topoisomerase I has been evaluated. Their cytotoxicities toward four tumor cell lines, one murine leukemia L1210 and three human tumor cell lines, one prostate carcinoma DU145, one colon carcinoma HT29, and one non-small cell lung carcinoma A549, have been determined. Their abilities to inhibit the checkpoint kinase Chk1 have been evaluated.
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