1,2,4-Trioxanes as potential antimalarial agents.
A number of 1,2,4-trioxanes were prepared and tested for antimalarial activity in search of a simplified analogue of the naturally occurring antimalarial qinghaosu. The compounds were assayed in an in vitro system for antimalarial activity against chloroquine-susceptible and chloroquine-resistant strains of Plasmodium falciparum. The most active compounds were methyl 2-(2,4a-epidioxy-4a,5,6,7,8,8a-hexahydro-5,5,8a-trimethyl-2H-1-benzop yra n-2-yl) acetate (3b), which showed IC20's of 96 and 39 ng/mL, respectively, and 2,4a-epidioxy-3,4,4a,5,6,7,8,8a-octahydro-2-[2-(benzoyloxy)propyl]-5,5,8 a- trimethyl-2H-1-benzopyran (12), which showed IC50's of 24 and 99 ng/mL, respectively. For comparison, qinghaosu exhibits an IC50 of 1 ng/mL for both strains.
Kepler
J A
JA
Research Triangle Institute, Research Triangle Park, North Carolina 27709.
Philip
A
A
Lee
Y W
YW
Morey
M C
MC
Carroll
F I
FI
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000627:therapeutic use; D037621:Artemisinins; D002738:Chloroquine / Q000627:therapeutic use; D004351:Drug Resistance; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002738:Chloroquine; C031327:artemisinin