Endoperoxides as potential antimalarial agents.
A number of mono- and bicyclic endoperoxides were prepared and tested for antimalarial activity in search of a simplified analogue of the 5-oxygen-substituted 1,2,4-trioxane ring structure 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 P. falciparum. The most active compound in this assay was 2-[((butyloxy)-carbonyl)oxy]-1,1,10-trimethyl-6,9-epidioxy-delta 7-octalin (17a), which showed an IC50 of 100 and 57 ng/mL, respectively. For comparison, qinghaosu exhibits a mean IC50 less than 3.4 ng/mL.
Kepler
J A
JA
Philip
A
A
Lee
Y W
YW
Musallam
H A
HA
Carroll
F I
FI
D000818:Animals; D000962:Antimalarials; D037621:Artemisinins; D055598:Chemical Phenomena; D002621:Chemistry; D004351:Drug Resistance; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010545:Peroxides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D010545:Peroxides; D012717:Sesquiterpenes; C031327:artemisinin