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 language | English |
---|---|
Pages (from-to) | 59-67 |
Number of pages | 9 |
Journal | Parasitology International |
Volume | 47 |
Issue number | 1 |
DOIs | |
Publication status | Published - Mar 1 1998 |
Keywords
- 5- Fluoroorotate
- Antimalarial agent
- Combination chemotherapy
- P. berghei
- P. falciparum
- Sulfamonomethoxine
ASJC Scopus subject areas
- Parasitology
- Infectious Diseases