A potent antimalarial activity of 5-fluoroorotate in combination with sulfamonomethoxine against Plasmodium falciparum in vitro and Plasmodium berghei in mice

Hye Sook Kim, Hirofumi Miyake, Meiji Arai, Yusuke Wataya

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The antimalarial activity of 5-fluoroorotate and sulfamonomethoxine, 4- amino-N-(6-methoxy-4-pyrimidinyl) benzenesulfonamide, was evaluated against Plasmodium falciparum in vitro and P. berghei in vivo. The concentrations of 5-fluoroorotate and sulfamonomethoxine required for 50% inhibition of growth (IC50) of P. falciparum were 4.8 nM and 1.2 μM, respectively. In vitro, a combination of 5-fluoroorotate with sulfamonomethoxine showed potent synergy: the required concentrations in combination for 5-fluoroorotate and sulfamonomethoxine were as low as 1/12 and 1/15 of the respective IC50 values. In vivo, although either 5-fluoroorotate or sulfamonomethoxine given orally reduced parasitemia, neither completely eliminated parasites from mice. In contrast, a combination of 5-fluoroorotate and sulfamonomethoxine produced a rapid decrease in parasitemia within 24 h and achieved complete cure of mice, with no parasite recrudescence or toxicity. These results suggest that a combination of 5-fluoroorotate and sulfamonomethoxine could form the basis of a new antimalarial combination for the treatment of human malaria.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalParasitology International
Volume47
Issue number1
DOIs
Publication statusPublished - Mar 1 1998

Keywords

  • 5- Fluoroorotate
  • Antimalarial agent
  • Combination chemotherapy
  • P. berghei
  • P. falciparum
  • Sulfamonomethoxine

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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