Ring-substituted 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides with similar patterns of cytotoxicity to the dual topo I/II inhibitor DACA

A series of ring-substituted analogues of the topoisomerase inhibitor 11-ox o-11H-indeno[1,2-b]quinoline-6-carboxamides was prepared and evaluated. The compounds were prepared by Pfitzinger reaction of the appropriate isatin-7 -carboxylic acids and 1-indanones, followed by selective thermal decarboxyl ation of the resulting tetracyclic diacids, subsequent oxidation of the met hylene group with alkaline permanganate under carefully controlled conditio ns, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were eval uated in a panel of cell lines in culture. The largest increases in cytotox icity (five to tenfold) were shown by 4-substituted analogues, with the 4-C l derivative having an IC50 of 8 nM against the Lewis lung carcinoma. (C) 1 999 Elsevier Science Ltd. All rights reserved.