Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in vitro. Some of the synthesized compounds exhibit high antifungal activity, both fungistatic and fungicidal, and lead to morphological changes in the Candida yeast cell wall. Based on the use of limited proteomic screening and toxicity analysis in mutants, we show that Mycosidine activity is associated with glucose transport. This suggests that this first-in-class antifungal drug has a novel mechanism of action that deserves further study.

Zn phthalocyanine with improved synthesis suitable for bulk production shows extremely high antimicrobial efficacies even under weak indoor light. The dye-impregnated cellulose material inactivates over 99.996% of drug-resistant C. albicans, S. aureus and E. faecalis in just one hour exposure with consumer-grade fluorescent lamps and diodes.

Polyene antifungal amphotericin B (AmB) has been used for over 60 years, and remains a valuable clinical treatment for systemic mycoses, due to its broad antifungal activity and low rate of emerging resistance. There is no consensus on how exactly it kills fungal cells but it is certain that AmB and the closely-related nystatin (Nys) can form pores in membranes and have a higher affinity towards ergosterol than cholesterol. Notably, the high nephro- and hemolytic toxicity of polyenes and their low solubility in water have led to efforts to improve their properties. We present the synthesis of new amphotericin and nystatin amides and a comparative study of the effects of identical modifications of AmB and Nys on the relationship between their structure and properties. Generally, increases in the activity/toxicity ratio were in good agreement with increasing ratios of selective permeabilization of ergosterol- vs. cholesterol-containing membranes. We also show that the introduced modifications had an effect on the sensitivity of mutant yeast strains with alterations in ergosterol biosynthesis to the studied polyenes, suggesting a varying affinity towards intermediate ergosterol precursors. Three new water-soluble nystatin derivatives showed a prominent improvement in safety and were selected as promising candidates for drug development.

A series of novel conjugates of cobalt bis(dicarbollide) and closo-dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to Bacillus cereus ATCC 10702 and are not active against Gram-negative microorganisms and Candida albicans at the maximum studied concentration of 1000 mg/L. The conjugate of alkynyl-curcumin with azide synthesized from the tetrahydropyran derivative of cobalt bis(dicarbollide) exhibited activity against Gram-positive microorganisms: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and the clinical isolate MRSA 17, that surpassed curcumin by 2–4 times.