SYNTHESIS AND ACTIVITY OF SOME ANTIMALARIAL BISQUINOLINES

A new type of bisquinoline antimalarial, in which the basic side chain of chloroquine is retained, has been evaluated. Nine bisamides were p repared from aliphatic diacids with 6-amino- and 4-(4-(diethylamino)-1 -methylbutyl)amino)quinoline, and screened against chloroquine-sensiti ve and -resistant strains of Plasmodium falciparum in vitro. The resis tance indices for all compounds were lower than for chloroquine. The p osition of attachment and length of the linker chain markedly affected activity. The most active (IC50 = 120 nM against the chloroquine-resi stant FAC8 strain) was the -(O)C(CH2)(4)C(O)- linked 8-amino compound.