DISPIRO-1,2,4,5-TETRAOXANES - A NEW CLASS OF ANTIMALARIAL PEROXIDES

被引:167
作者
VENNERSTROM, JL
FU, HN
ELLIS, WY
AGER, AL
WOOD, JK
ANDERSEN, SL
GERENA, L
MILHOUS, WK
机构
[1] UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL,CTR TROP PARASIT DIS,MIAMI,FL 33177
[2] WALTER REED ARMY MED CTR,DEPT EXPTL THERAPEUT,WASHINGTON,DC 20307
[3] UNIV NEBRASKA,DEPT CHEM,OMAHA,NE 68182
关键词
D O I
10.1021/jm00094a015
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50's comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.
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页码:3023 / 3027
页数:5
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