The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novel cis-fused cyclopenteno derivatives.
The new Chinese antimalarial blood schizontocide, artemisinin, derived from the plant Artemisia annua, displays a high level of activity against polyresistant Plasmodium falciparum. Several synthetic 1,2,4-trioxanes were examined in a search for compounds that exhibit a similar type of action against drug-resistant parasites. This paper, the first of a series, describes the examination of these trioxanes against drug-sensitive and drug-resistant malaria parasites in a rodent model, using artemisinin and arteether as comparison standards. Cis-fused cyclohexeno-1,2,4-trioxanes (10-17) substituted with various side-chains revealed for the most part variable but weak antimalarial activity. On the other hand, cis-fused cyclopenteno-1,2,4-trioxanes (18-19) showed greater activity, 19 showing about 1/30th of the activity of arteether against drug-sensitive Plasmodium berghei in vivo, thereby providing a clue to the structure-activity relationship.
Peters
W
W
CAB International Institute of Parasitology, St. Albans, Hertfordshire, U.K.
Robinson
B L
BL
Rossier
J C
JC
Jefford
C W
CW
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D000081005:Cyclohexane Monoterpenes; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D005260:Female; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D039821:Monoterpenes; D009281:Naphthalenes / Q000627:therapeutic use; D015125:Oxyquinoline / Q000627:therapeutic use; D010545:Peroxides; D010666:Phenylpropionates / Q000627:therapeutic use; D010962:Plasmodium berghei / Q000187:drug effects* / Q000302:isolation & purification; D013729:Terpenes / Q000627:therapeutic use
D000962:Antimalarials; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D009281:Naphthalenes; D010545:Peroxides; D010666:Phenylpropionates; D013729:Terpenes; C043372:ascaridole; D015125:Oxyquinoline; C047854:fenozan