Introduction. The main mechanism of action of all antifungal azoles (imidazoles, triazoles,
and thiazoles) is inhibition of 14-α-demethylase, a cytochrome P450 enzyme (CYP51) that
catalyzes the removal of the C-14α-methyl group from lanosterol. The inhibition occurs due to
binding of the free nitrogen atom of the azole group to the iron of heme’s prostetic group in the
active site of the enzyme. Recently, a good review on sterol 14-α-demethylase inhibitors has been
published by Leaver. The property of 1, 2, 4-triazol derivatives to inhibit the biosynthesis of
ergosterins stimulated the intensive search of new active compounds.
Purpose of the study. Continuing our studies of N-viny-1, 2, 4-triazoles, we have
synthesized a series of alkyl-aryl-N-vinyl-1, 2, 4-triazoles with potential antifungal activity.
Materials and methods. The reaction proceeds with the interaction of ketones (1) with
various aldehydes (2) in the presence of a catalyst, under conditions of reaction of Knoevenagel.
The yield of the final product varies from 75 to 92%.
Results and discussions. The structure of synthesized compounds was determined by
physical methods (NMR , IR, and X-Ray spectroscopy). The antifungal activity was evaluated
against eight different fungal species: Aspergillus fumigatus, A. versicolor, A. ochramensis, A.
niger, Trichoderma viride, Penicillium funiculosum, P. ochrochloron, P. verrucosum var.
cyclopium. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration have
been determined for each compound against all eight fungal strains.
Conclusions. The evaluation of antifungal activity revealed that all compounds showed
good antifungal activity with MIC values ranging from 0.02 mM to 0.52 mM and MFC from 0.03
mM to 0.52 mM better than reference drugs ketoconazole (MIC and MFC values at 0.28-1.88 mM
and 0.38 mM to 2.82 mM respectively) and bifonazole (MIC and MFC values at 0.32-0.64 mM and
0.64-0.81 mM).