Hostname: page-component-77c89778f8-cnmwb Total loading time: 0 Render date: 2024-07-20T18:06:25.977Z Has data issue: false hasContentIssue false
  • English
  • Français

Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity

Published online by Cambridge University Press:  06 April 2009

A. T. Hudson ,
A. W. Randall ,
M. Fry ,
C. D. Ginger ,
B. Hill ,
V. S. Latter ,
N. McHardy  and
R. B. Williams
A. T. Hudson
Affiliation:
Department of Therapeutic Chemistry, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
A. W. Randall
Affiliation:
Department of Therapeutic Chemistry, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
M. Fry
Affiliation:
Department of Biochemical Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
C. D. Ginger
Affiliation:
Department of Biochemical Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
B. Hill
Affiliation:
Department of Biochemical Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
V. S. Latter
Affiliation:
Department of Biochemical Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
N. McHardy
Affiliation:
Department of Biochemical Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3B8
R. B. Williams
Affiliation:
Department of Veterinary Research, Weilcome Research Laboratories, Berkhamsted, Herts HP4 2QE
Get access Rights & Permissions [Opens in a new window]

Extract

Novel hydroxynaphthoquinones are reported with outstanding efficacy against Plasmodium, Eimeria and Theileria species. Biochemical evidence is presented for the selective toxicity of these compounds being due to inhibition of parasite respiratory systems.

Type
Research Article
Information
Parasitology , Volume 90 , Issue 1 , February 1985 , pp. 45 - 55
Copyright
Copyright © Cambridge University Press 1985

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Boehm, P., Cooper, K., Hudson, A. T., Elphick, J. P. & McHardy, N. (1981). In vitro activity of 2-alkyl-3-hydroxy-1, 4-naphthoquinones against Theileria parva. Journal of Medicinal Chemistry 24, 295–9.CrossRefGoogle ScholarPubMed
Bustamante, E., Soper, J. W. & Pederson, P. L. (1977). A high-yield preparative method for isolation of rat liver mitochondria. Analytical Biochemistry 80, 401–8.CrossRefGoogle ScholarPubMed
Desjardins, R. E., Canfield, C. J., Haynes, J. D. & Chulay, J. D. (1979). Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrobial Agents and Chemotherapy 16 710–18.CrossRefGoogle ScholarPubMed
Fawaz, G. & Haddad, F. S. (1951). The effect of lapinone (M-2350) on P. vivax infections in man. American Journal of Tropical Medicine and Hygiene 31, 569–71.CrossRefGoogle Scholar
Fieser, L. F., Chang, F. C., Dauben, W. G., Heidelberger, C., Heymann, H. & Selioman, A. M. (1948). Naphthoquinone antimalarials. XVIII. Metabolic oxidation products. Journal of Pharma cology and Experimental Therapeutics 94, 85–96.Google Scholar
Fry, M.& Williams, R. B. (1984). Effects of decoquinate and clopidol on electron transport in mitochondria of Eimeria tenella (Apicomplexa: Coccidia). Biochemical Pharmacology 33, 229–4.CrossRefGoogle ScholarPubMed
Fulton, J. D. & Spooner, D. F. (1960). Metabolic studies on Toxoplasma gondii. Experimental Parouitology 9, 293–301.CrossRefGoogle ScholarPubMed
Gregory, K. G. & Peters, W. (1970). The chemotherapy of rodent malaria IX. Causal prophylaxis. Part I. A method for demonstrating drug action on exoerythrocytic stages. Annals of Tropical Medicine and Parasitology 64, 15–24.CrossRefGoogle Scholar
Gutteridge, W. E., Dave, D. & Richards, W. H. G. (1979). Conversion of dihydroorotate to orotate in parasitic protozoa. Biochimica et Biophysica Acta 582, 390–401.CrossRefGoogle ScholarPubMed
Herrmann, E. C., Dunn, J. H. & Schmidt, R. R. (1973) DEAE-paper chromatography to separate intermediates of the pyrimidine biosynthetic pathway and to assay aspartate transcarbamylase and dihydroorotase activities. Analytical Biochemistry 53, 478–83.CrossRefGoogle ScholarPubMed
Hudson, A. T. (1984). Lapinone, menoctone, hydroxyquinolinequinones and similar structures. In Handbook of Experimental Pharmacology, Vol. 68/II, Antimalarial Drugs (ed. Peters, W. and Richards, W. H. O.), pp. 343–361. Berlin, Heidelberg and New York: Springer-Verlag.Google Scholar
Hudson, A. T. & Randall, A. W. (1982 a). European Patent Application No. 0–077–551.Google Scholar
Hudson, A. T. & Randall, A. W. (1982 b). European Patent Application No. 0–077–550.Google Scholar
Jaffe, J. J. & Gutteridge, W. E. (1974). Purine and pyrimidine metabolism in protozoa. Actualités Protozoologiques 1, 23–5.Google Scholar
Latter, V. S. & Wilson, R. G. (1979). Factors influencing the assessment of anticoccidial activity in cell culture. Parasitology 79, 169–75.CrossRefGoogle ScholarPubMed
McHardy, N. (1978). In vitro studies on the action of menoctone and other compounds on Theileria parva and T. annulata. Annals of Tropical Medicine and Parasitology 72, 501–11.CrossRefGoogle ScholarPubMed
McHardy, N., Haigh, A. J. B. & Dolan, T. T. (1976s). Chemotherapy of Theileria parva infection. Nature London 261, 698–9.CrossRefGoogle ScholarPubMed
McHardy, N., Hudson, A. T., Morgan, D. W. T., Rae, D. O. & Dolan, T. T. (1983). Activity of 10 naphthoquinones, including parvaquone (993C) and menoctone, in cattle artificially infected with Theileria parva. Research in Veterinary Science 35, 347–52.CrossRefGoogle ScholarPubMed
McHardy, N. & Rae, D. O. (1981). Treatment of stabilate-induced East Coast fever with menoctone. Tropical Animal Health and Production 13, 227–39.CrossRefGoogle ScholarPubMed
Nyormoi, O., Bwayo, J. J. & Hirumi, H. (1981). Theileria parva: Isolation of macroschizonts from in vitro propagated lymphoblastoid cells of cattle. Experimental Parasitology 52, 303–11.CrossRefGoogle ScholarPubMed
Olenick, J. G. (1979). 2-Hydroxy-3-alkyl-1,4-naphthoquinones. In Antibiotics, Vol. V/2. Mechanism of Action of Antieukaryotic and Antiviral Compounds (ed. Hahn, F. E.), pp. 214–222. Berlin, Heidelberg and New York: Springer-Verlag.Google Scholar
Porter, T. H. & Folkers, K. (1974). Antimetabolites of coenzyme Q. Their potential application as anti-malarials. Angewandte Chemie 13, 559–618.CrossRefGoogle Scholar
Rogers, E. F. (1967). United States Patent Application No. 3–347–742.Google Scholar
Sarett, L. H. (1968). United States Patent Application No. 3–367–830.Google Scholar
Schmidt, L. H., Fradkin, R., Genther, C. S., Rossan, R. N. & Squires, W. (1982). Plasmodium cynomolgi infections in the rhesus monkey. II. Responses of sporozoite-induced and trophozoite induced infections to standard antimalarial drugs. American Journal of Tropical Medicine and Hygiene 31 646–65.CrossRefGoogle Scholar
Smithers, G. W., Gero, A. M. & O'Sullivan, W. J. (1978). A simple radio assay for dihydroorotate dehydrogenase. Analytical Biochemistry 88 94–103.CrossRefGoogle Scholar
Thurston, J. P. (1950). The action of antimalarial drugs infected with Plasmodium berghei. British Journal of Pharmacology and Chemotherapy 5 409–16.CrossRefGoogle ScholarPubMed
Trager, W.& Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–5.CrossRefGoogle ScholarPubMed
Williams, R. B. (1973). Effects of different infection rates on the oocyst production of Eimeria acervulina or Bimeria tenella in the chicken. Parasitology 67 279–88.CrossRefGoogle ScholarPubMed
World Health Organization (1973). Chemotherapy of malaria and resistance to antimalarials. WHO Technical Report Series No. 529.Google Scholar