Therapeutic efficacies of GW471552 and GW471558, two new azasordarin derivatives, against pneumocystosis in two immunosuppressed-rat models.
Two new azasordarins, GW471552 and GW471558, were studied in vivo for treatment of Pneumocystis carinii pneumonia. In the Wistar rat spontaneous pneumonia model, both azasordarins significantly reduced the number of P. carinii cysts per gram of lung homogenate when administered at 1 mg/kg of body weight twice a day for 10 days. In a nude rat inoculation model, both compounds showed therapeutic efficacy at 0.25 mg/kg twice a day for 10 days.
GlaxoSmithKline, Technological Park of Madrid, Severo Ochoa 2, 28760 Tres Cantos, Madrid., Spain. dgv28867@gsk.com
Elena
E
Jimenez
Antonio
A
Martínez
El Moukhtar
el M
Aliouat
Jesus
J
Caballero
Eduardo
E
Dei-Cas
Domingo
D
Gargallo-Viola
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007192:Indenes; D008168:Lung / Q000382:microbiology; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D011010:Pneumocystis / Q000187:drug effects; D016720:Pneumocystis Infections / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D017208:Rats, Wistar
D000935:Antifungal Agents; C445683:GW 471552; C433787:GW 471558; D007192:Indenes; D009025:Morpholines