Abstract

The polyene macrolide antibiotics have been used in an-tifungal therapy since first o f them were discovered in 1950's. Up to now, four polyene macrolides are being used in medical practice, namely amphotericin B, nystatin, candi-cidin and pimaricin.The antifungal activity and mode of ac-tion of polyene macrolides is determined by their structure, chemical and physical properties.The main fragment of polyene macrolide molecule is the macrocyclic ring built of two different regions. One fragment is hydrophobic, where an unsaturated polyene chromophore is located and on the other side a number of hydroxyl groups and "polar head" constitute a hydrophilic region. The number of conjugated double bonds in the chromophore determines a characteristic UV absorption spectra of the molecule which is represented by three peaks. According to that, amphotericin B and candicidin are both classificated as heptaenes, while nystatin as tetraene or a "degenerated heptaene". This multifunctional and large ring structure of the antibiotics causes many prob-lems in everyday usage. They are very poorly soluble in water, and can easily form aggregates in aqueous media. Polyene antibiotics exhibit also poor stability to heat, UV radiation and extremes of pH. As solids they are relatively stable but in aqueous solution, stability is much lower.In our work we examined the stability of three macrolides: amphotericin B, candicidin and nystatin complex from different sources. Our research was focused on structural changes induced by different factors like temperature, pH, solvents or exposition to light and UV radiation. We re-lated results of physico-chemical experiments to biological activity of this antifungal agents, to compare which envi-ronmental factor have the most influence on antimicrobial activity. The physical and chemical damages where studied by absorption spectroscopy and HPLC analysis conjugated with mass spectrometry. The results showed that nystatin is the least stable compound in the series and the exposition to different environment factors cause the conformational modifications that effect in lower biological activity.

Authors (4)