Search

Synthesis of β-hydroxysulfides of 1,3-dioxepane series and their further functionalization were performed. Chiral β-hydroxysulfides were separated into enantiomers using enzymatic acylation by lipase PS. Study of antifungal activity of the obtained compounds showed that some enantiomerically pure 6-arylthio-1,3-dioxepan-5-ols represent promising antifungal drug candidates.

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 antibacterial in vitro activity, 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 and Escherichia 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.

A series of trans-6-phenylethenyl substituted pyridoxine derivatives, novel bioisosteric analogs of drugs based on trans-stilbene scaffold, were synthesized using the Wittig reaction of a bis-triphenylphosphonium pyridoxine derivative with various aromatic aldehydes. Two compounds demonstrated high activity against the estrogen-dependent MCF-7 (breast cancer) cell line with IC50 in the range of 1.9–7.9 µM and very good selectivity for other studied normal and tumor cells, including the estrogen receptor negative MDA-MB-231 breast cancer cells. The active compounds possessed an intense blue fluorescence, and this feature allowed us to effectively visualize them in cytoplasm and in nucleus. The obtained results make the described chemotype a promising starting point for the development of new anticancer agents for the therapy of estrogen-dependent malignancies.