New tissue schizontocidal antimalarial drugs

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

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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
Issue number3
StatePublished - 1981

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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