Synthesis and in vitro antimalarial activity of some indolo[3,2-c]quinolines

Abstract

A series of indolo[3,2-c]quinolines (1b-e) was synthesized by Fischer indolization of 7-chloro-1,2,3,4-tetrahydroquinolin-4-one with the appropriate hydrazines (7b-e). Evaluation of in vitro antimalarial activity was carried out against a chloroquine resistant strain of Plasmodium falciparum. Except for compound 1e which lacked a basic side chain at position 9, the other indolo[3,2-c]quinolines 1b-d were active. The most active compound was 3-chloro-8-methoxy-9-(4-methyl-1-piperazinylmethyl)-11H-indolo[3,2-c]quinoline (1d) trihydrochloride which was about 104 times more active than chloroquine in vitro. The effects of structural variation on antimalarial activity were discussed. © 1992.