Synthesis and cytotoxic activity of N -(2-Diethylamino)ethylcarboxamide and other derivatives of 10 H -Quindoline Academic Article uri icon

abstract

  • A series of mono- and dimeric N-methylquindoline carboxamides were prepared by Friedlander condensation between methyl 2-amino-3-formyl benzoate and 3-acetoxy-1-acetylindoles, followed by exhaustive methylation with methyl iodide to give N-methylquindoline esters. Direct amination of these, or hydrolysis to the acids and amine coupling via intermediate imidazolides gave the desired carboxamides. The compounds were evaluated in a panel of cell lines in culture. The monomeric compounds showed similar structure-activity relationships to the known indeno[1,2-b]quinolines, with a 4-methyl group increasing potency several-fold. Bis analogues linked through the carboxamide were more cytotoxic than the corresponding monomers in the human leukemia lines, but N-N linked dimers were generally less potent, except for a tetracationic derivative. The most potent monomeric analogue showed moderate growth delay (ca. 5 days) against sub-cutaneously implanted colon 38 tumors in mice.

authors

  • Chen, Junjie
  • Deady, Leslie W
  • Kaye, Anthony J
  • Finlay, Graeme J
  • Baguley, Bruce C
  • Denny, William A

publication date

  • July 2002