Synthesis of indolo[3,2- c]quinolines and indolo[3,2- d]benzazepines and their interaction with DNA

Abstract

A number of indolo[3,2- c]quinolines and tetrahydroindolo[3,2- d]-1-benzazepines were synthesised by Fischer indolisation of ketones including 7-chloro-1,2,3,4-tetrahydroquinol-4-one and 8-chloro-2,3,4,5-tetrahydro-1-benzazepin-5-one with several hydrazines. Some of the planar indolo[3,2- c]quinoline derivatives were shown by their effects on DNA supercoiling to form intercalation complexes with DNA and to inhibit the synthesis of macromolecules in cultured KB cells. Non-planar tetrahydroindolo[3,2- d]-1-benzazepines did not form intercalation complexes with DNA under the same conditions. 3a, b, d inhibited the synthesis of macromolecules in cultured KB cells, 3a being the most effective. No significant anti-tumor activity was detected for 3a, b, 4a, e in the NIH screening program.