In vitro and in vivo candicidal activities of 2-(p-n-hexylphenylamino)-1,3-thiazoline.
The 2-amino-1,3-thiazoline, 2-(p-n-hexylphenylamino)-1,3-thiazoline (MDL 20,245) killed 10(5) logarithmic or stationary phase Candida albicans/ml in less than 1 h. Miconazole killed logarithmic phase cells at that rate, but miconazole, clotrimazole or econazole killed stationary phase cells at a slower rate of 10(2)-10(4) cells/ml in 24 h. MDL 20,245 induced efflux of K+ and L[U-14C] lysine from C. albicans, indicating that the candicidal mechanism is to exert direct damage upon the cytoplasmic membrane. The activity of MDL 20,245 in vitro was antagonized by fatty acids, triglycerides and phospholipids. Topical application of MDL 20,245 ointment (10% w/v) twice per day for 4 days to rats suppressed C. albicans-induced vaginitis 100%. Single-dose regimens of MDL 20,245, miconazole or clotrimazole correlated with 97, 90 and 73% suppression, respectively. These data suggest that MDL 20,245 may be effective in the treatment of C. albicans-induced vaginitis in humans.
Baumann
R J
RJ
Marion Merrell Dow Research Institute, Cincinnati, Ohio.
Mayer
G D
GD
Fite
L D
LD
Gill
L M
LM
Harrison
B L
BL
D000287:Administration, Topical; D000818:Animals; D002176:Candida albicans / Q000187:drug effects*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology; D003022:Clotrimazole / Q000494:pharmacology; D015169:Colony Count, Microbial; D005260:Female; D008825:Miconazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014627:Vaginitis / Q000188:drug therapy* / Q000382:microbiology
D013844:Thiazoles; C070919:2-(4-n-hexylphenylamino)-1,3-thiazoline; D008825:Miconazole; D003022:Clotrimazole