Anticandidial effect of phenylbutene derivatives and their interaction with ergosterol

This paper reports the effect of phenylbut-3-en-2-one, of its analogues, be aring 3-nitro, 4-nitro, 4-chloro- and 4-dimethylamino substituents at the p henyl moiety, and of the hydrazide, phenylhydrazide and oxime of 4-nitrophe nylbut-3-en-2-one on the growth and germ-tube formation of Candida spp., as well as their ability to interact with ergosterol in water/dimethylformami de (DMF) solution and their acute toxicity for mice. 3-Nitro-, 4-nitro- and 4-chlorophenylbul-3-en-2-ones inhibit candidial growth in vitro in concent rations ranging from 0.01 to >0.4 mM and their activity is comparable to th at of ketoconazole (in mg/l) and lower than that of amphotericin B. The res t of the compounds are inactive at >0.4 mM. Germ-tube forma tion of C. albi cans is inhibited at 0.04 mM 4-nitrophenylbut-3-en-2-one and at 0.005 mM of the 3-nitro isomer. A decrease in the absorption maxima in ergosterol mixt ures with 4-dimethyl amino, 3-nitrophenylbut-3-en-2-one and the oxime of th e 4-nitrophenylbut-3-en-2-one was observed, indicative of interaction in wa ter/DMF solutions, while no changes in the UV spectra of the remaining comp ounds were detectable. That suggests that the growth inhibiting effect is n ot in correlation with their ability to interact with ergosterol. despite t he resemblance to polyenes. LD50 for mice is 367 mg/kg for 4-nitrophenylbut -3-en-2-one and 395 mg/kg for the 3-nitro isomer.