In vitro and in vivo studies with flutrimazole, a new imidazole derivative with antifungal activity.
1-[(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) is a new topical imidazole antifungal agent which displays potent broad-spectrum in vitro activity against dermatophytes, filamentous fungi and yeasts, saprophytic and pathogenic to animals and humans (MIC = 0.025-5.0 micrograms/ml). In most of these studies the activity of flutrimazole was comparable to that of clotrimazole and markedly higher than that of bifonazole (MIC differences of greater than or equal to 1 order of magnitude). Tested against Scopulariopsis brevicaulis (8 strains), both flutrimazole and clotrimazole exhibited fungistatic and fungicidal activity, and clotrimazole appeared something less active (MIC = 0.3-2.5 micrograms/ml) than flutrimazole (MIC = 0.15-0.6 micrograms/ml). In animal experiments, topical application of 1% and 2% flutrimazole, as a cream or solution, was highly effective in models of rat vaginal candidiasis and guinea-pig trichophytosis, giving a rate of cured or cured plus markedly improved animals higher than 80%. Flutrimazole shares the mode of action of other imidazole or triazole-containing antifungals, i.e. inhibition of fungal lanosterol 14 alpha-demethylase, as it strongly inhibits ergosterol biosynthesis in a cell-free homogenate of Candida albicans, with an IC50 value of 0.071 mumol/l.
García Rafanell
J
J
Research Center, J. Uriach & Cía, S.A., Barcelona, Spain.
Dronda
M A
MA
Merlos
M
M
Forn
J
J
Torres
J M
JM
Zapatero
M I
MI
Basi
N
N
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy / Q000382:microbiology; D003022:Clotrimazole / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005658:Fungi / Q000187:drug effects*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D014005:Tinea / Q000188:drug therapy / Q000382:microbiology
D000935:Antifungal Agents; D007093:Imidazoles; C076986:flutrimazole; D003022:Clotrimazole; C036596:bifonazole