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 |
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Keywords
- 5- Fluoroorotate
- Antimalarial agent
- Combination chemotherapy
- P. berghei
- P. falciparum
- Sulfamonomethoxine
ASJC Scopus subject areas
- Parasitology
- Infectious Diseases
Cite this
A potent antimalarial activity of 5-fluoroorotate in combination with sulfamonomethoxine against Plasmodium falciparum in vitro and Plasmodium berghei in mice. / Kim, Hye-Sook; Miyake, Hirofumi; Arai, Meiji; Wataya, Yusuke.
In: Parasitology International, Vol. 47, No. 1, 01.03.1998, p. 59-67.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A potent antimalarial activity of 5-fluoroorotate in combination with sulfamonomethoxine against Plasmodium falciparum in vitro and Plasmodium berghei in mice
AU - Kim, Hye-Sook
AU - Miyake, Hirofumi
AU - Arai, Meiji
AU - Wataya, Yusuke
PY - 1998/3/1
Y1 - 1998/3/1
N2 - 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.
AB - 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.
KW - 5- Fluoroorotate
KW - Antimalarial agent
KW - Combination chemotherapy
KW - P. berghei
KW - P. falciparum
KW - Sulfamonomethoxine
UR - http://www.scopus.com/inward/record.url?scp=0031969322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031969322&partnerID=8YFLogxK
U2 - 10.1016/S1383-5769(98)00003-8
DO - 10.1016/S1383-5769(98)00003-8
M3 - Article
AN - SCOPUS:0031969322
VL - 47
SP - 59
EP - 67
JO - Parasitology International
JF - Parasitology International
SN - 1383-5769
IS - 1
ER -