Abstract
We have shown previously that chloroquine and amodiaquine inhibit the glutathione-dependent degradation of ferriprotoporphyrin IX (FP). We have also demonstrated that treatment of human erythrocytes infected with Plasmodium falciparum with chloroquine or amodiaquine results in a dose- and time-dependent accumulation of FP in the membrane fraction of these cells in correlation with parasite killing. High levels of membrane FP are known to perturb the barrier properties of cellular membranes, and could thereby irreversibly disturb the ion homeostasis of the parasite and cause parasite death. We here report on the effect of various 4-aminoquinolines, as well as pyronaridine, halofantrine and some bis-quinolines, on glutathione-mediated destruction of FP in aqueous solution, when FP was bound non-specifically to a protein, and when it was dissolved in human erythrocyte ghost membranes. We showed that all drugs were capable of inhibiting FP degradation in solution. The inhibitory efficacy of some drugs declined when FP was bound non-specifically to protein. Quinine and mefloquine were unable to inhibit the degradation of membrane-associated FP, in line with their inability to increase membrane-associated FP levels in malaria-infected cells following drug treatment. The discrepancy between chloroquine and amodiaquine on the one hand, and quinine and mefloquine on the other, is discussed in terms of the particular location of drugs and FP in the phospholipid membrane, and may suggest differences in the mechanistic details of the antimalarial action of these drugs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.