Evaluation of some adamantane-based synthetic trioxanes against Plasmodium knowlesi in rhesus monkeys.
In our search for synthetic substitutes for artemisinin and its derivatives we had earlier prepared a series of adamantane-based 1, 2, 4-trioxanes 5a-c which had shown promising activity against P. berghei in Swiss mice. We have further evaluated these and two new compounds (5d-e) against Plasmodium knowlesi W1, a virulent malaria parasite in rhesus monkeys, in the dose range of 40-80 mg/kg x 5 days by intramuscular route. Trioxanes 5b and 5c showed 100% protection and cure at 80 mg/kg x 5 days, while trioxane 5a showed 71% cure at this dose. Detailed studies again showed 50% curative effect of 5a at 40 mg/kg x 5 days treatment.
Tripathi
Renu
R
Division of Parasitology, Central Drug Research Institute, Lucknow-226001, India. renu1113@rediffmail.com
Mishra
Dhermendra
D
Rizvi
Amber
A
Singh
Chandan
C
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D016790:Plasmodium knowlesi; D012008:Recurrence
D000962:Antimalarials; D000218:Adamantane