Skip to main content
NCBI home page
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 1987;65(3):381–386.

Chloroquine resistance of Plasmodium berghei: biochemical basis and countermeasures*

R I Salganik, T G Pankova, T V Chekhonadskikh, T M Igonina
PMCID: PMC2491009  PMID: 3117393

Abstract

Microsomal monooxygenases, enzymes that metabolize xenobiotics, may be responsible for the chloroquine resistance of malarial parasites. Plasmodium cells contain cytochrome P-450 and exhibit aryl hydrocarbon hydroxylase and aminopyrine N-dimethylase activity, two monooxygenases that inactivate chloroquine. The activities of these monooxygenases are considerably higher in chloroquine-resistant strains of Plasmodium berghei than in the chloroquine-sensitive strain of the parasite. Inhibitors of microsomal monooxygenases have the potential to overcome the chloroquine resistance of Plasmodium spp., and, of those inhibitors tested, the copper-lysine complex, copper(lysine)2, was the most effective.

Full text

PDF
381

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DePierre J. W., Moron M. S., Johannesen K. A., Ernster L. A reliable, sensitive, and convenient radioactive assay for benzpyrene monooxygenase. Anal Biochem. 1975 Feb;63(2):470–484. doi: 10.1016/0003-2697(75)90371-1. [DOI] [PubMed] [Google Scholar]
  3. Doberstyn E. B. Resistance of Plasmodium falciparum. Experientia. 1984 Dec 15;40(12):1311–1317. doi: 10.1007/BF01951884. [DOI] [PubMed] [Google Scholar]
  4. Halpert J., Neal R. A. Inactivation of purified rat liver cytochrome P-450 by chloramphenicol. Mol Pharmacol. 1980 May;17(3):427–431. [PubMed] [Google Scholar]
  5. Howells R. E., Peters W., Homewood C. A., Warhurst D. C. Theory for the mechanism of chloroquine resistance in rodent malaria. Nature. 1970 Nov 14;228(5272):625–628. doi: 10.1038/228625a0. [DOI] [PubMed] [Google Scholar]
  6. Kato R., Takanaka A., Shoji H. Inhibition of drug-metabolizing enzymes of liver microsomes by hydrazine derivatives in relation to their lipid solubility. Jpn J Pharmacol. 1969 Jun;19(2):315–322. doi: 10.1254/jjp.19.315. [DOI] [PubMed] [Google Scholar]
  7. NASH T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J. 1953 Oct;55(3):416–421. doi: 10.1042/bj0550416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964 Jul;239:2370–2378. [PubMed] [Google Scholar]
  9. Popova V. I., Leonova I. N., Weiner L. M., Salganik R. I. Interaction of the substrate analogue of cytochrome P-450 and mixed function oxidases. Biochem Pharmacol. 1982 Jun 1;31(11):1993–1998. doi: 10.1016/0006-2952(82)90411-7. [DOI] [PubMed] [Google Scholar]
  10. Richards W. H., Williams S. G. The removal of leucocytes from malaria infected blood. Ann Trop Med Parasitol. 1973 Jun;67(2):249–250. doi: 10.1080/00034983.1973.11686885. [DOI] [PubMed] [Google Scholar]
  11. Rumiantseva G. V., Vainer L. M. Vzaimodeistvie kompleksa Cu(Lys) 2 a NADPH-zavisimoi mikrosomal'noi tsep'iu perenosa élektronov i mikrosomal'noi membranoi. Biokhimiia. 1982 Jun;47(6):921–930. [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES