Reversal of chloroquine resistance in murine malaria parasites by prostaglandin derivatives.
An oligomeric ester of prostaglandin B2 (OC-5186) was found to reverse chloroquine resistance in the murine malarial parasite Plasmodium berghei. When mice were infected with either chloroquine-sensitive or -resistant P. berghei on day 0 (by intraperitoneal injection of 1 x 10(6) parasitized erythrocytes), they died before day 23. When treated with 15 mg/kg/day of chloroquine for the first four days of infection, all mice infected with the sensitive-strain survived, while all those infected with the resistant strain died before day 23. When OC-5186 (3-12 mg/kg/day) was administered in combination with chloroquine for the first four days, 60% of the animals infected with the resistant strain survived. The differences in the survival rate between the group treated with chloroquine only and the group treated with a combination of drugs (chloroquine plus 3-12 mg/kg/day of OC-5186) were significant. There was also a significant inhibition of parasitemia in the group treated with the combination of drugs. The combinations of chloroquine and a monomer ester of prostaglandin B2 (OC-5181) had some antimalarial activity, but the differences between the chloroquine-treated group and the combination treatment group were not significant in terms of both the parasitemia and the survival rate. Another oligomeric ester of prostaglandin E1 (MR-356) as well as unesterified monomer prostaglandins (PGA2 and PGB2) were ineffective by themselves and in combination with chloroquine.
Central Drug Research Institute, Lucknow, India.
S
S
Chandra
S T
ST
Ohnishi
B N
BN
Dhawan
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D011454:Prostaglandins A / Q000494:pharmacology / Q000627:therapeutic use; D011456:Prostaglandins B / Q000494:pharmacology / Q000627:therapeutic use*
D000962:Antimalarials; D011454:Prostaglandins A; D011456:Prostaglandins B; C060276:MR 356; C070097:OC 5186; C081762:OC 5181; D002738:Chloroquine; C042026:prostaglandin B2; D000527:Alprostadil; C100008:prostaglandin A2