Kinetic modelling of the response of Plasmodium falciparum to chloroquine and its experimental testing in vitro
作者： Timothy G. Geary , Alan D. Divo , James B. Jensen , Marina Zangwill , Hagai Ginsburg
DOI: 10.1016/0006-2952(90)90302-2
关键词:
摘要: The antimalarial mode of action chloroquine (CQ) has been investigated in great detail recent years, but the overall mechanism is still controversial. Instead further probing molecular aspects partial reactions, a model based on weak base properties CQ and its delta pH-driven accumulation acid parasite compartments devised, integrated response to drug under different experimental conditions assayed verify validity model. Factors such as inoculum size (parasitemia.hematocrit) medium pH were altered using CQ-sensitive (FCC1) -resistant (FCR3, VNS) isolates Plasmodium falciparum. Experimental results full agreement with predictions model, implying that therapeutic concentrations do not raise food vacuole, i.e. alkalinization an insufficient explanation for activity CQ, there no need invoke active QC efflux pump explain resistance. Calculations data demonstrate resistance correlated higher and/or intracellular target concentration vacuole. also have implications design interpretation vitro inhibitory tests.
elsevier.com
sci-hub.se 参考文章(28)
A. Yayon, Z.I. Cabantchik, H. Ginsburg, Identification of the acidic compartment of Plasmodium falciparum-infected human erythrocytes as the target of the antimalarial drug chloroquine. The EMBO Journal. ,vol. 3, pp. 2695- 2700 ,(1984) , 10.1002/J.1460-2075.1984.TB02195.X
P. Nguyen-Dinh, D. Payne, Pyrimethamine sensitivity in Plasmodium falciparum: determination in vitro by a modified 48-hour test. Bulletin of The World Health Organization. ,vol. 58, pp. 909- 912 ,(1980)
Phuc Nguyen-Dinh, William Trager, Plasmodium falciparum in vitro: determination of chloroquine sensitivity of three new strains by a modified 48-hour test. American Journal of Tropical Medicine and Hygiene. ,vol. 29, pp. 339- 342 ,(1980) , 10.4269/AJTMH.1980.29.339
CarlosC. Campbell, WilliamE. Collins, William Chin, StevenM. Teutsch, DelynnM. Moss, CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM FROM EAST AFRICA:: Cultivation and Drug Sensitivity of the Tanzanian I/CDC Strain from an American Tourist The Lancet. ,vol. 314, pp. 1151- 1154 ,(1979) , 10.1016/S0140-6736(79)92383-3
Hagai Ginsburg, Timothy G. Geary, Current concepts and new ideas on the mechanism of action of quinoline-containing antimalarials Biochemical Pharmacology. ,vol. 36, pp. 1567- 1576 ,(1987) , 10.1016/0006-2952(87)90038-4
Bruce G. Weniger, Richard S. Blumberg, Carlos C. Campbell, Thomas C. Jones, Dwight L. Mount, Stephen M. Friedman, High-level chloroquine resistance of Plasmodium falciparum malaria acquired in Kenya. The New England Journal of Medicine. ,vol. 307, pp. 1560- 1562 ,(1982) , 10.1056/NEJM198212163072506
D. Krogstad, I. Gluzman, D. Kyle, A. Oduola, S. Martin, W. Milhous, P. Schlesinger, Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance Science. ,vol. 238, pp. 1283- 1285 ,(1987) , 10.1126/SCIENCE.3317830
SA Adelusi, AH Dawodu, LA Salako, Kinetics of the uptake and elimination of chloroquine in children with malaria. British Journal of Clinical Pharmacology. ,vol. 14, pp. 483- 487 ,(1982) , 10.1111/J.1365-2125.1982.TB02016.X
IraK. Schwartz, CarlosC. Campbell, David Payne, Omar Juma Khatib, IN-VIVO AND IN-VITRO ASSESSMENT OF CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM MALARIA IN ZANZIBAR The Lancet. ,vol. 321, pp. 1003- 1005 ,(1983) , 10.1016/S0140-6736(83)92640-5
Avner Yayon, Hagai Ginsburg, The transport of chloroquine across human erythrocyte membranes is mediated by a simple symmetric carrier. Biochimica et Biophysica Acta. ,vol. 686, pp. 197- 203 ,(1982) , 10.1016/0005-2736(82)90113-4