TY - JOUR
T1 - Differential effects of 4-aminoquinoline-containing antimalarial drugs on hemoglobin digestion in Plasmodium falciparum-infected erythrocytes
AU - Famin, Oleg
AU - Ginsburg, Hagai
PY - 2002/2/1
Y1 - 2002/2/1
N2 - Several reports suggest that the antimalarial mode of action of quinoline drugs may differ in their mechanistic details. The malaria parasite Plasmodium falciparum was treated in culture with chloroquine, amodiaquine, quinine and mefloquine in a dose- and time-dependent fashion. After removal of the drug, the viability of the parasites and their hemoglobin content were determined. Whereas in the presence of chloroquine and amodiaquine, there was a correlation between parasite killing and accumulation of hemoglobin, with quinine and mefloquine parasite killing was not associated with the accumulation of hemoglobin. Mefloquine inhibited the chloroquine-dependent accumulation of hemoglobin. It is suggested that whereas chloroquine and amodiaquine inhibit the digestion of hemoglobin, mefloquine and possibly quinine inhibit the ingestion of host cell hemoglobin by interfering with the ingestion process. These results may explain the demonstrable antagonism between chloroquine and mefloquine and their antipodal sensitivity to these drugs.
AB - Several reports suggest that the antimalarial mode of action of quinoline drugs may differ in their mechanistic details. The malaria parasite Plasmodium falciparum was treated in culture with chloroquine, amodiaquine, quinine and mefloquine in a dose- and time-dependent fashion. After removal of the drug, the viability of the parasites and their hemoglobin content were determined. Whereas in the presence of chloroquine and amodiaquine, there was a correlation between parasite killing and accumulation of hemoglobin, with quinine and mefloquine parasite killing was not associated with the accumulation of hemoglobin. Mefloquine inhibited the chloroquine-dependent accumulation of hemoglobin. It is suggested that whereas chloroquine and amodiaquine inhibit the digestion of hemoglobin, mefloquine and possibly quinine inhibit the ingestion of host cell hemoglobin by interfering with the ingestion process. These results may explain the demonstrable antagonism between chloroquine and mefloquine and their antipodal sensitivity to these drugs.
KW - Chloroquine
KW - Malaria
KW - Mefloquine
KW - Mode of action
KW - Plasmodium falcifarum
UR - http://www.scopus.com/inward/record.url?scp=0036471447&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(01)00878-4
DO - 10.1016/S0006-2952(01)00878-4
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C2 - 11853690
AN - SCOPUS:0036471447
SN - 0006-2952
VL - 63
SP - 393
EP - 398
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 3
ER -