Synthesis and biological evaluation of 6-(9-hydroxy-5-methyl (and 5,6-dimethyl)-6H-pyrido[4,3-b]carbazol-1-yl)picolinic amides as new olivacine derivatives.
Starting from 2-(6-methoxy-1-methylcarbazol-2-yl)ethylamine and diethyl-2,6-pyridine dicarboxylate, the title compounds were obtained through five or six steps. The new compounds retained significant cytotoxicity towards various tumor cell lines, but in vivo studies on murine P388 leukemia, B16 melanoma and Lewis lung carcinoma showed a lowered antitumor activity with respect to that of the related olivacine lead compound 1.
Landras
C
C
UMR 176 CNRS, Synthèse Organique, Institut Curie Recherche, Orsay, France.
Jasztold-Howorko
R
R
Pierré
A
A
Léonce
S
S
Guilbaud
N
N
Kraus-Berthier
L
L
Guillonneau
C
C
Rolland
Y
Y
Atassi
G
G
Bisagni
E
E
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011725:Pyridines; D004317:Doxorubicin