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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 16期

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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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.

引用

页码：3023 / 3027

页数：5