2-(fluoromethyl)dehydroornithine-methyl-ester and alpha-(difluoromethyl)arginine

DFMO (difluoromethylornithine) and DFMA (difluoromethylarginine), irreversible suicide inhibitors of ornithine and arginine decarboxylase activities (ODC and ADC) respectively, inhibit the growth of six species of Microsporum and six species of Trichophyton. Trichophyton species in general, are more sensitive than Microsporum species. DFMA inhibits growth as effectively as DFMO but at a 10-fold lower concentration. Inhibition is specific, as a number of substrates and end products of ODC and ADC activities antagonize DFMA and DFMO (i.e. ornithine greater than putrescine = spermidine greater than agmatine). The methylester analogue of ornithine, MFMOme (monofluormethyldehydroornithine methylester) is at least a 25-fold more effective inhibitor than DFMO; the inhibition is specific as it is reversed by ornithine.

Topics: Antifungal Agents; Arginine; Arthrodermataceae; Carboxy-Lyases; Eflornithine; Microbial Sensitivity Tests; Microsporum; Ornithine Decarboxylase Inhibitors; Polyamines; Trichophyton