The Basis of Antimalarial Action: Non-Weak Base Effects of Chloroquine on Acid Vesicle pH
- 1 March 1987
- journal article
- research article
- Published by American Society of Tropical Medicine and Hygiene in The American Journal of Tropical Medicine and Hygiene
- Vol. 36 (2), 213-220
- https://doi.org/10.4269/ajtmh.1987.36.213
Abstract
Biologically active concentrations of chloroquine increase the pH of the parasite's acid vesicles within 3–5 min. This increase in pH results from two mechanisms, one of which is markedly reduced in chloroquine-resistant parasites. Because chloroquine is a weak base, it increases vesicle pH by that mechanism in chloroquine-susceptible and resistant parasites and mammalian cells (based on its two pKs and on the ΔpH between the acid vesicle and the extracellular environment). In chloroquine-susceptible parasites, but not resistant parasites or mammalian cells, chloroquine increases the pH of acid vesicles 700- to 800-fold more than can be accounted for by its properties as a weak base. The increase in acid vesicle pH caused by these non-weak base effects of nanomolar chloroquine in susceptible parasites suggests that chloroquine acts by interfering with acid vesicle functions in the parasite such as the endocytosis and proteolysis of hemoglobin, and the intracellular targeting of lysosomal enzymes. The non-weak base effects of nanomolar chloroquine on parasite vesicle pH are also responsible for its safety because these chloroquine concentrations do not affect mammalian cells.This publication has 35 references indexed in Scilit:
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