Syntheses and antiproliferative activities of rebeccamycin analogues bearing two 7-azaindole moieties.
As a part of structure-activity relationship studies on rebeccamycin analogues, compounds containing two aza-indole moieties were synthesized bearing either a methyl group or a hydrogen atom on the imide nitrogen. The azaindole substructures were expected to enhance the cytotoxicity toward tumor cell lines through stronger hydrogen bonding with the target enzyme(s). The cytotoxicities of compounds 8, 10 and 19 against a panel of tumor cell lines were examined and compared with those of rebeccamycin, dechlorinated rebeccamycin 2 and N-methylated analogue A. Their effect on the L1210 cell cycle was also evaluated. Compound 19, having an imide NH function had the strongest cytotoxicity towards L1210 cells and induced the largest accumulation of cells in the G2+M phases of the cell cycle. In contrast to their non-aza analogues, which were cytotoxic for all the cell lines tested, diaza compounds 10 and 19 showed selectivity for some cell lines.
Marminon
Christelle
C
Université Blaise Pascal, Synthèse Et Etude de Systèmes à Intérêt Biologique, UMR 6504, 63177 Aubière, France.
Pierré
Alain
A
Pfeiffer
Bruno
B
Pérez
Valérie
V
Léonce
Stéphane
S
Renard
Pierre
P
Prudhomme
Michelle
M
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002227:Carbazoles; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D007202:Indicators and Reagents; D007211:Indoles; D009005:Monosaccharides; D000644:Quaternary Ammonium Compounds; C053339:rebeccamycin; C009405:tetrabutylammonium