Treatment of experimental Pneumocystis carinii pneumonia with analogs of pentamidine.
Seven analogs of pentamidine were tested for their activity against an immunosuppressed rat model of Pneumocystis carinii pneumonia. Structural alterations of the pentamidine molecule included variations of the alkyl chain linking the two p-amidino phenoxy moieties and relocation of the amidine groups from the para to the meta position on the phenoxy rings. All analogs of pentamidine were active against P. carinii pneumonia when compared to a saline-treated control group. One derivative, 1, 4-di(4'-amidinophenoxy)butane, proved to be statistically more active than the parent drug.
Tidwell
R R
RR
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Kilgore
S G
SG
Ohemeng
K A
KA
Geratz
J D
JD
Hall
J E
JE
D000578:Amidines / Q000627:therapeutic use*; D000818:Animals; D004247:DNA / Q000378:metabolism; D008297:Male; D010419:Pentamidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors
D000578:Amidines; D014361:Trypsin Inhibitors; D010419:Pentamidine; D004247:DNA; D013940:Thymidylate Synthase