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

abstract

  • A series of ring-substituted analogues of the topoisomerase inhibitor 11-oxo-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 decarboxylation of the resulting tetracyclic diacids, subsequent oxidation of the methylene group with alkaline permanganate under carefully controlled conditions, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were evaluated in a panel of cell lines in culture. The largest increases in cytotoxicity (five to tenfold) were shown by 4-substituted analogues, with the 4-Cl derivative having an IC50 of 8 nM against the Lewis lung carcinoma.

authors

  • Deady, Leslie W
  • Desneves, José
  • Kaye, Anthony J
  • Thompson, Michelle
  • Finlay, Graeme J
  • Baguley, Bruce C
  • Denny, William A

publication date

  • December 1999