A mechanism for the synergistic antimalarial action of atovaquone and proguanil

Antimicrobial Agents and Chemotherapy

Volumn 43, Issue 6, 1999, Pages 1334-1339

  Srivastava, Indresh K ^a,b   Vaidya, Akhil B ^a  

^a DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ATOVAQUONE; BIGUANIDE; CITRININ; MYXOTHIAZOL; PROGUANIL; PYRIMETHAMINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; DRUG EFFECT; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENTIATION; DRUG SELECTIVITY; ELECTRON TRANSPORT; FEMALE; MALE; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; MOUSE; NEWBORN; NONHUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL;

EID: 0033063070     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/aac.43.6.1334     Document Type: Article

References (42)

1. Araujo, F. G., J. Huskinson, and J. S. Remington. 1991. Remarkable in vitro and in vivo activities of 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob. Agents Chemother. 35:293-299.
2. Birkett, D. J., D. Rees, T. Andersson, F. J. Gonzalez, J. O. Miners, and M. E. Veronese. 1994. In vitro activation of proguanil to cycloguanil by human liver microsomes is mediated by CYP3A isoforms as well as by S-mephenytoin hydrokylase. Br. J. Clin. Pharmacol. 37:413-420.
3. 1 complex. Biochim. Biophys. Acta 1275:61-69.
4. Canfield, C. J., M. Pudney, and W. E. Gutteridge. 1995. Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro. Exp. Parasitol. 80:373-381.
5. Carrington, H. C., A. F. Crowther, D. G. Davey, A. A. Levi, and F. L. Rose. 1951. A metabolite of "Paludrine" with high antimalarial activity. Nature 168:1080.
6. Chance, B., and G. R. Williams. 1955. A simple and rapid assay of oxidative phosphorylation. Nature 175:1120-1121.
7. Chiodini, P. L., C. P. Conlon, D. B. Hutchinson, J. A. Farquhar, A. P. Hall, T. E. Peto, H. Birley, and D. A. Warrell. 1995. Evaluation of atovaquone in the treatment of patients with uncomplicated Plasmodium falciparum malaria. J. Antimicrob. Chemother. 36:1073-1078.
8. Crowther, A. F., and A. A. Levi. 1953. Proguanil - the isolation of a metabolite with high antimalarial activity. Br. J. Pharmacol. 8:93-97.
9. Dunn, C. J., and D. H. Peters. 1995. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 49:721-749.
10. Eling, W. 1977. Ficoll fractionation for the separation of parasitized erythrocytes from malaria infected blood. Bull. W. H. O. 55:105-114.
11. Fidock, D. A., and T. E. Wellems. 1997. Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect intrinsic activity of proguanil. Proc. Natl. Acad. Sci. USA 94:10931-10936.
12. Foote, S. J., D. Galatis, and A. F. Cowman. 1990. Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. Proc. Natl. Acad. Sci. USA 87:3014-3017.
13. Fry, M., E. Webb, and M. Pudney. 1990. Effect of mitochondrial inhibitors on adenosinetriphosphate levels in Plasmodium falciparum. Comp. Biochem. Physiol. 968:775-782.
14. Fry, M., and M. Pudney. 1992. Site of action of the antimalarial hydroxynapthoquinone, 2-[-4-(4′-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-napthoquinone (566C80). Biochem. Pharmacol. 43:1545-1553.
15. Gulleridge, W. E., D. Dave, and W. H. G. Richards. 1979. Conversion of dihydroorotate to orotate in parasitic protozoa. Biochim. Biophys. Acta 582:390-401.
16. Hammond, D. J., J. R. Burchell, and M. Pudney. 1985. Inhibition of pyrimidine biosynthesis de novo by 2-(4-t-butylcyclohexyl)-3-hydroxy-1,4,napthoquinone in vitro. Mol. Biochem. Parasitol. 14:97-109.
17. Helsby, N. A., S. A. Ward, R. E. Howell, and A. M. Breckenridge. 1990. The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism. Br. J. Clin. Pharmacol. 30:287-291.
18. Helsby, N. A., G. Edwards, A. M. Breckenridge, and S. A. Ward. 1993. The multiple dose pharmacokinetics of proguanil. Br. J. Clin. Pharmacol. 35:653-656.
19. Hudson, A. T., A. W. Randall, C. D. Ginger, B. Hill, V. S. Latter, N. McHardy, and R. B. Williams. 1985. Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoan activity. Parasitology 90:45-55.
20. Hudson, A. T., M. Dickins, C. D. Ginger, W. E. Gutteridge, T. Holdrich, D. B. A. Hutchinson, M. Pudney, A. W. Randall, and V. S. Latter. 1991. 566C80: a broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. Drugs Exp. Clin. Res. 17:427-435.
21. Hudson, A. T. 1984. Lapinone, menoctone, hydroxyquinolinequinones and similar structures, p. 343-361. In W. Peters and W. H. G. Richards (ed.), Handbook of experimental pharmacology, vol. 68. Antimalarial drugs. Springer-Verlag, New York, N.Y.
22. Hughes, W. T., V. L. Gray, W. E. Gutteridge, V. S. Latter, and M. Pudney. 1990. Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii. Antimicrob. Agents Chemother. 34:225-228.
23. Kovacs, J. A. 1992. Efficacy of atovaquone in treatment of toxoplasmosis in patients with AIDS. Lancet 340:637-688.
24. Kusaka, M., R. Setiabudy, K. Chiba, and T. Ishizaki. 1996. Simultaneous measurements of proguanil and its metabolites in human plasma and urine by reversed-phase high performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4′-hydroxylation status. Am. J. Trop. Med. Hyg. 54:189-196.
25. Looareesuwan, S., C. Viravan, H. K. Webester, D. E. Kyle, D. B. A. Hutchinson, and C. J. Canfield. 1996. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am. J. Trop. Med. Hyg. 54:62-66.
26. McNally, J., S. M. O'Donovan, and J. P. Dalton. 1992. Plasmodium berghei and Plasmodium chabaudi chabaudi: development of simple in vitro erythrocyte invasion assays. Parasitology 105:355-362.
27. Peters, W. 1990. Plasmodium: resistance to antimalarial drugs. Ann. Parasitol. Hum. Comp. 65(Suppl. 1):103-106.
28. Peterson, D. S., W. K. Milhous, and T. E. Wellems. 1990. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc. Natl. Acad. Sci. USA 87:3018-3022.
29. Radloff, P. D., J. Philipps, M. Nkeyi, D. B. A. Hutchinson, and P. G. Kremsner. 1996. Atovaquone and proguanil for Plasmodium falciparum malaria. Lancet 340:1511-1514.
30. Reeder, J. C., K. H. Rieckmann, B. Genton, K. Lorry, B. Wines, and A. F. Cowman. 1997. Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea. Am. J. Trop. Med. Hyg. 55:209-213.
31. Schafer, G. 1969. Site specific uncoupling and inhibition of oxidative phosphorylation by biguanides. Biochim. Biophys. Acta 172:334-337.
32. Schafer, G. 1983. Biguanides, a review of history, pharmacodynamics and therapy. Diabetes Metab. 9:148-163.
33. Srivastava, I. K., J. M. Morrisey, E. Darrouzet, F. Daldal, and A. B. Vaidya. Submitted for publication.
34. Srivastava, I. K., H. Rottenberg, and A. B. Vaidya. 1997. Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in malaria parasites. J. Biol. Chem. 272:3961-3966.
35. Vaidya, A. B. 1998. Mitochondrial physiology as a target for atovaquone and other antimalarials, p. 355-368. In I. W. Sherman (ed.), Malaria: parasite biology, pathogenesis, and protection. ASM Press, Washington, D.C.
36. Vaidya, A. B., M. S. Lashgari, L. G. Pologe, and J. Morrisey. 1993. Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Mol. Biochem. Parasitol. 58:33-42.
37. Ward, S. A., N. A. Helsby, E. Skjelbo, K. Brosen, L. F. Gram, and A. M. Breckenridge. 1991. The activation of the biguanide antimalarial proguanil co-segregates with mephenytoin oxidation polymorphism - a panel study. Br. J. Clin. Pharmacol. 31:689-692.
38. Wendel, W. B. 1946. The influence of naphthoquinones upon the respiratory and carbohydrate metabolism of malaria parasites. Fed. Proc. 5:406-407.
39. Wernsdorfer, W. H., and D. Payne. 1991. The dynamics of drug resistance in Plasmodium falciparum. Pharmacol. Ther. 50:95-121.
40. Wiselogle, F. Y. (ed.). 1946. A survey of antimalarial drugs 1941-1945, vol. 1. Edwards, Ann Arbor, Mich.
41. Wright, J. D., N. A. Helsby, and S. A. Ward. 1995. The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides. Br. J. Clin. Pharmacol. 39:441-444.
42. 1 complex from bovine heart mitochondria. Science 277:60-66.