New 1H-1,2,4-Triazolyl Derivatives as Antimicrobial Agents.

New 1H-1,2,4-triazolyl derivatives were synthesized, and six of them were selected based on docking prediction for the investigation of their antimicrobial activity against five bacterial and eight fungal strains. All compounds demonstrated antibacterial activity with MIC lower than that of the ampicillin and chloramphenicol. In general, the most sensitive bacteria appeared to be P. fluorescens, while the plant pathogen X. campestris was the most resistant. The antifungal activity of the compounds was much better than the antibacterial activity. All compounds were more potent (6 to 45 times) than reference drugs ketoconazole and bifonazole with the best activity achieved by compound 4 a. A. versicolor, A. ochraceus, A.niger, and T.viride showed the highest sensitivity to compound 4 b, while, T. viride, P. funiculosum, and P.ochrochloron showed good sensitivity to compound 4 a. Molecular docking studies suggest that the probable mechanism of antibacterial activity involves the inhibition of the MurB enzyme of E. coli, while CYP51 of C. albicans appears to be involved in the mechanism of antifungal activity. It is worth mentioning that none of the tested compounds violated Lipinski's rule of five.

Ectonucleotidase Inhibitory and Redox Activity of Imidazole-Based Organic Salts and Ionic Liquids.

Cytotoxicity against cancer and normal cells, inhibition of ectonucleotidase, and redox properties of a new group of imidazole-based organic salts and ionic liquids were studied. The tetrachloroferrate salt of a 1-methylimidazole derivative of salicylic aldehyde had most prominent inhibitory activity against ectonucleotidase as well as a higher cytotoxicity against HeLa cells and lower cytotoxicity against BHK-21 cells than the reference compound carboplatin. The studied compounds exhibited a moderate level of antioxidant activity with better results for the salicylic aldehyde derivatives than for spiropyrans. Moreover, these compounds did not generate singlet oxygen.

Recent advances in the use of cyclodextrins in antifungal formulations.

Cyclodextrins are usually used in antifungal formulations as auxiliary substances to improve solubility, stability, or other physicochemical properties of the active compound. Nevertheless, more and more research and practical use results indicate that cyclodextrins might also act as active compounds in pharmaceutical formulations. The biological effects of cyclodextrins, important for their use within antimycotic formulations, can be divided into: effects based on the ability of cyclodextrins to form inclusion complexes with endogenous substances (membrane lipids, cellular cholesterol), effects based on formation of inclusion complexes with component parts of fungi cells, and effects based on the chemical nature of cyclodextrins and their derivatives. This review will cover the advances in research of biological activity of cyclodextrins with focus on their properties responsible for their synergistic effect with antimycotic compounds.

Highly enantio- and diastereoselective generation of two quaternary centers in spirocyclopropanation of oxindole derivatives.

Spirocyclopropanes: Only one out of eight possible stereoisomers was obtained in the asymmetric cascade cyclopropanation of alkylidene oxindoles with ethyl 2-chloroacetoacetate. Improved catalyst design ensured that spirocyclopropyl oxindoles featuring two quaternary centers were synthesized in high yield and high enantio- and diastereoselectivity (see scheme).