Lack of Cross-Resistance to 4-Aminoquinolines in Chloroquine-Resistant Plasmodium falciparum In vitro

The potencies of 10 quinoline-containing antimalarials, including chloroquine, amodiaquine, CM-2,999-2K, quinine, mefloquine, SN-6911, SN-11875, SN-12108, SN-12308, and SN-12309, were determined in vitro against five strains of Plasmodium falciparum characterized in vivo and in vitro by various degrees of sensitivity to chloroquine. These strains included the chloroquine-sensitive strains Honduras and FCC1, and R1-resistant line FCR3TC, and the R3-resistant strains FCR1 and Viet Nam Smith (VNS). The potency of chloroquine varied 100-fold in these strains, with minimum inhibitory concentrations (MIC) ranging from 3.2 X 10(-9) M in FCC1 to 3.2 X 10(-7) M in FCR1. The other drugs had different patterns; SN-12108 had an MIC of 3.2 X 10(-9) M in FCC1, Honduras, and FCR1, and 3.2 X 10(-8) M in VNS. However, SN-6911 (3-methylchloroquine), amodiaquine, and mefloquine showed little or no variation in potency among these strains. There was no correlation between sensitivity to chloroquine and any other drug. This lack of cross-resistance in vitro must be taken into account in consideration of theories of chloroquine action in these parasites.