Ferriprotoporphyrin IX (FP) and a chloroquine-FP complex lysed isolated Plasmodium falciparum parasites as judged by decreases in the turbidity of parasite suspensions and by ultrastructural changes. Exposure of parasite suspensions to 50 microM FP or to a complex formed from 50 microM FP and 20 MicroM chloroquine reduced the number of identifiable parasites and caused swelling and loss of internal detail in those that were identifiable. The amount of lysis was dose-dependent over the range of 10 to 50 microM FP. Formation of a chloroquine-FP complex reduced, but did not eliminate, the toxicity of FP. Since there is evidence indicating that a chloroquine-FP complex forms when chloroquine-susceptible parasites are exposed to chloroquine, we suggest that accumulation of this complex may account for the chemotherapeutic effect of chloroquine against P. falciparum.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC182018 | PMC |
| http://dx.doi.org/10.1128/AAC.21.5.819 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study.
J Inorg Biochem
December 2011
Department of Chemistry, McGill University, Montreal, Canada.
To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine-FP complex is not μ-oxo dimeric indicating that the hypothesis that chloroquine binds to FP μ-oxo dimer with a stoichiometry of 1 chloroquine:2 μ-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine.
View Article and Find Full Text PDFSolution behavior of hematin under acidic conditions and implications for its interactions with chloroquine.
J Biol Inorg Chem
September 2010
La Trobe Institute for Molecular Science and Centre of Excellence for Coherent X-ray Science, La Trobe University, Melbourne, VIC, 3086, Australia.
During the intraerythrocytic stage of its lifecycle, the malaria parasite digests host erythrocyte hemoglobin, producing free ferriprotoporhyrin IX (FP). Crystallization of FP into hemozoin is essential for its detoxification and is the target of quinoline antimalarials. To gain further insight into the mechanism of hemozoin formation and quinoline action we have studied the behavior of FP and related derivatives in 40% methanol in water at different concentrations across a broad pH range (2-12).
View Article and Find Full Text PDFFerriprotoporphyrin IX (FP) is released from hemoglobin by oxidative denaturation or by proteolytic degradation. FP added exogenously to cells or released intracellularly is a lytic toxin. Chloroquine enhances the accumulation of exogenous FP in cellular membranes and potentiates its lytic effect.
View Article and Find Full Text PDFBovine serum albumin and preparations of cell sap from malaria parasites and normal erythrocytes were tested for ability to protect cellular membranes against the toxicity of ferriprotoporphyrin IX (FP) and a chloroquine-FP complex. Suspensions of Plasmodium berghei (approximately 7 X 10(6) parasites per ml, isolated from saponin-lysed, infected erythrocytes) were used as a test system. Toxicity was monitored by measuring changes in turbidity of these suspensions at 700 nm.
View Article and Find Full Text PDFLysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex.
Antimicrob Agents Chemother
May 1982
Ferriprotoporphyrin IX (FP) and a chloroquine-FP complex lysed isolated Plasmodium falciparum parasites as judged by decreases in the turbidity of parasite suspensions and by ultrastructural changes. Exposure of parasite suspensions to 50 microM FP or to a complex formed from 50 microM FP and 20 MicroM chloroquine reduced the number of identifiable parasites and caused swelling and loss of internal detail in those that were identifiable. The amount of lysis was dose-dependent over the range of 10 to 50 microM FP.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!