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Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterialin vitroactivity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine) and antibacterial/antiseptic (miramistin, benzalkonium chloride) agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci andEscherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms.

An efficient synthesis of novel 6-substituted derivatives of pyridoxine was achieved. The reactions of various thiols with mono-, bis-, and tris(сhlorine) derivatives of 6-methyl-2,3,4-tris(hydroxymethyl)pyridin-5-ol (6-hydroxymethylpyridoxine) gave sulfur-containing derivatives of pyridoxine.

Derivatives bearing 1,2 or 3 chloro substituents are prepared and used as starting materials for different types of title compounds.

Both the endo- and exo-isomers of epoxy acetals (II)/(III) are reacted with thiophenol to afford corresponding hydroxy sulfides, which are further transformed in search for new antimycotic substances.

Both exo- and endo-isomers of 4-phenyl-3,5,8-trioxabicyclo[5.1.0]octane were reacted with thiophenol to afford individual diastereomers of hydroxy sulfides which were further processed in search for new antimycotic substances.