Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.
A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position (on a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice.
Deady
L W
LW
Department of Chemistry, La Trobe University, Bundoora, Victoria, Australia. L.Deady@latrobe.edu.au
Desneves
J
J
Kaye
A J
AJ
Finlay
G J
GJ
Baguley
B C
BC
Denny
W A
WA
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
C431771:11-oxo-11H-indeno(1,2-b)quinolinecarboxamide; D000577:Amides; D000970:Antineoplastic Agents; D007192:Indenes; D011804:Quinolines