New tissue schizontocidal antimalarial drugs

D. E. Davidson, Arba L Ager, J. L. Brown, F. E. Chapple, R. E. Whitmire, R. N. Rossan

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Over 700 causal prophylactic and radical curative antimalarial drugs have been discovered during the screening of approximately 4000 chemical compounds in rodent and simian malaria models. Causal prophylactic activity in the Plasmodium berghei rodent model was demonstrated by 10 distinct groups of chemicals: 1) tetrahydrofolate dehydrogenase inhibitors, 2) naphthoquinones, 3) dihydroacridinediones, 4)tetrahydrofurans, 5) guanylhydrazones, 6) analogues of clopidol, 7) quinoline esters, 8) dibenzyltetrahydropyrimidine, 9) 6-aminoqinolines, 10) 8-aminoquinolines. Of the causal prophylactic compounds only the 6- and 8- aminoquinolines were capable of curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys. The 6-aminoquinolines were substantially less active than primaquine. This report describes a series of 4-methyl-5-phenoxy-6-methoxy-8-aminoquinolines, which are potent blood schizontocides and radical curative drugs. The most active member of this series, 4-methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8[(4-amino-1-methylbutyl)amino]quinoline succinate (WR 225448), was 5 times more active than primaquine in curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys. As a blood schizontocide, WR 225448 was effective in animal models against P. berghei P. cynomolgi, P. vivax, and both drug-sensitive and drug-resistant strains of P. falciparum. WR 225448 was also more toxic than primaquine in rats on subacute (28 day) administration.

Original languageEnglish (US)
Pages (from-to)463-479
Number of pages17
JournalBulletin of the World Health Organization
Volume59
Issue number3
StatePublished - 1981
Externally publishedYes

Fingerprint

Antimalarials
Primaquine
Plasmodium berghei
Macaca mulatta
Clopidol
Rodentia
Pharmaceutical Preparations
Furans
Naphthoquinones
Tetrahydrofolate Dehydrogenase
Poisons
Succinic Acid
Infection
Malaria
Esters
Animal Models
WR 225448
8-aminoquinoline
6-aminoquinoline

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Davidson, D. E., Ager, A. L., Brown, J. L., Chapple, F. E., Whitmire, R. E., & Rossan, R. N. (1981). New tissue schizontocidal antimalarial drugs. Bulletin of the World Health Organization, 59(3), 463-479.

New tissue schizontocidal antimalarial drugs. / Davidson, D. E.; Ager, Arba L; Brown, J. L.; Chapple, F. E.; Whitmire, R. E.; Rossan, R. N.

In: Bulletin of the World Health Organization, Vol. 59, No. 3, 1981, p. 463-479.

Research output: Contribution to journalArticle

Davidson, DE, Ager, AL, Brown, JL, Chapple, FE, Whitmire, RE & Rossan, RN 1981, 'New tissue schizontocidal antimalarial drugs', Bulletin of the World Health Organization, vol. 59, no. 3, pp. 463-479.
Davidson DE, Ager AL, Brown JL, Chapple FE, Whitmire RE, Rossan RN. New tissue schizontocidal antimalarial drugs. Bulletin of the World Health Organization. 1981;59(3):463-479.
Davidson, D. E. ; Ager, Arba L ; Brown, J. L. ; Chapple, F. E. ; Whitmire, R. E. ; Rossan, R. N. / New tissue schizontocidal antimalarial drugs. In: Bulletin of the World Health Organization. 1981 ; Vol. 59, No. 3. pp. 463-479.
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