Activity of two chlorinated lincomycin analogues against chloroquine-resistant falciparum malaria in owl monkeys.
The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4'-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria.
D000818:Animals; D002713:Chlorine / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance; D000882:Haplorhini; D008034:Lincomycin / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy*; D010963:Plasmodium falciparum; D013997:Time Factors
D002713:Chlorine; D002738:Chloroquine; D008034:Lincomycin