TY - JOUR
T1 - Potentiation of the antimalarial agent rufigallol
AU - Winter, R. W.
AU - Cornell, Kenneth A.
AU - Johnson, Linda L.
AU - Ignatushchenko, Marina
AU - Hinrichs, David J.
AU - Riscoe, Michael K.
PY - 1996/6
Y1 - 1996/6
N2 - We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine- resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar analysis was ~60-fold for experiments initiated with asynchronous parasites. The most pronounced synergism was observed in experiments with synchronized trophozoite-infected erythrocytes, in which the degree of synergy was at least 300-fold. While the mechanism underlying this drug potentiation remains unresolved, it is hypothesized that rufigallol acts in pro-oxidant fashion to produce oxygen radicals inside parasitized erythrocytes. These radicals would attack exifone, thereby initiating its transformation into a more potent compound, a xanthone.
AB - We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine- resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar analysis was ~60-fold for experiments initiated with asynchronous parasites. The most pronounced synergism was observed in experiments with synchronized trophozoite-infected erythrocytes, in which the degree of synergy was at least 300-fold. While the mechanism underlying this drug potentiation remains unresolved, it is hypothesized that rufigallol acts in pro-oxidant fashion to produce oxygen radicals inside parasitized erythrocytes. These radicals would attack exifone, thereby initiating its transformation into a more potent compound, a xanthone.
UR - http://www.scopus.com/inward/record.url?scp=0029890690&partnerID=8YFLogxK
U2 - 10.1128/aac.40.6.1408
DO - 10.1128/aac.40.6.1408
M3 - Article
C2 - 8726010
AN - SCOPUS:0029890690
SN - 0066-4804
VL - 40
SP - 1408
EP - 1411
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 6
ER -