Conformational and structural features determining in vitro antimalarial activity in some indolo[3,2-c]quinolines, anilinoquinolines and tetrahydroindolo[3,2-d]benzazepines

Abstract

A series of indolo[3,2-c]quinolines, anilinoquinolines and tetrahydroindolo[3,2-d]benzazepines, which differ in the conformational planarity of the key nuclei and the distance (N...N+) between the ring and side-chain nitrogen atoms, have been synthesized and evaluated in vitro against a number of isolates of Plasmodium falciparum. The results show that differences in conformational planarity of the indolo[3,2-c]quinoline (rigid), anilinoquinoline (flexible) and tetrahydroindolo[3,2-d]benzazepine (semi-rigid) nuclei have little effect on activity. However, the N...N+ distance is an important determinant of activity and analogues with a distance comparable to the N...N+ distance of amodiaquine and chloroquine demonstrated antimalarial activity. © 1994.