Abstract
It is established that high rates of morbidity and mortality caused by fungal infections are related to the current limited number of antifungal drugs and the toxicity of these agents. Imidazolium salts as azole derivatives can be successfully used in the treatment of fungal infections in humans. Steroid-functionalized imidazolium salts were synthesized using a new, more efficient method. As a result, 20 salts were obtained with high yields, 12 of which were synthesized and characterized for the first time. They were derivatives of lithocholic acid and 3-oxo-23,24-dinorchol-4-ene-22-al and were fully characterized by 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high resolution mass spectrometry (HRMS). Due to the excellent activity against bacteria and Candida albicans, new research was extended to include tests on five species of pathogenic fungi and molds: Aspergillus niger ATCC 16888, Aspergillus fumigatus ATCC 204305, Trichophyton mentagrophytes ATCC 9533, Cryptococcus neoformans ATCC 14116, and Microsporum canis ATCC 11621. The results showed that the new salts are almost universal antifungal agents and have a broad spectrum of activity against other human pathogens. To initially assess the safety of the synthesized salts, hemocompatibility with host cells and cytotoxicity were also examined. No toxicity was observed at the concentration at which the compounds were active against pathogens.
Highlights
Published data has indicated that the high rates of morbidity and mortality from fungal infections are related to the current limited number of antifungal drugs and the toxicity of the agents [1]
We recently described the synthesis and antimicrobial activity of two series of steroidbased imidazolium salts [34], which were derived from lithocholic acid and one of lithocholic acid metabolites [35] 3-oxo-23,24-dinorchol-4-en-22-al (1 and 2, Figure 2)
Our results indicated high antimicrobial efficacy of synthesized salts against the above-mentioned microorganism, with low hemolytic activity at a concentration that restricts the growth of hemolysis were indicated during antibiotic therapy, including β-lactams and polypeptides used in the treatment of infections caused by S. aureus, as well as in polyenes, which of are used in the case of fungal infection caused by Candida spp. and molds. 8Our results indicated high antimicrobial efficacy of synthesized salts against the above-mentioned microorganism, with low hemolytic activity at a concentration that restricts the growth of the microorganisms and allows achieving a therapeutic efficacy corresponding to the minimum inhibitory concentration (MIC)
Summary
Published data has indicated that the high rates of morbidity and mortality from fungal infections are related to the current limited number of antifungal drugs and the toxicity of the agents [1]. To address the aforementioned problems, researchers have attempted to find a strategy to improve treatment using various approaches. One of these is the modification of the chemical structure of traditional antifungals. It has been established that the above approaches can significantly enhance their activity and improve pharmacokinetic parameters [3]. Another important aspect is the development of new formulations for antifungal agents; many years
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