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Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
Abstract
In the last few years,increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds whichare highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and other adverse effects. In addition, the frequent use of available fungistatic drugs promotes drug resistance. Therefore, there is an urgent need for the development of a novel antifungal drug with a different mechanism of action, blocking of the fungal DNA topoisomerases activity appear to be a promising idea. According to previous studies on the m-AMSA moderate inhibitory effect on fungal topoisomerase II, we have decided to study Capridine β (also acridine derivative)antifungal activity,as well as its inhibitory potential on yeast topoisomerase II (yTOPOII). Results indicated that Capridineβantifungal activity depends on the kind of strains analyzed (MICs range 0.5–64μgmL−1) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus Candida albicanswas performed. IE1 exhibited no activity against fungal cells due to an inability to enter thecells. Although no antifungal activity was observed, in contrast to Capridine β, biotransformation metabolite totally inhibited the yTOPOII-mediated relaxation at concentrations lower than detected for m-AMSA. The closely related Capridine βonly slightly diminished the catalytic activity of yTOPOII.
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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Pathogens
no. 10,
ISSN: 2076-0817 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Gabriel I., Rząd K., Paluszkiewicz E., Kozłowska-Tylingo K.: Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity// Pathogens -Vol. 10,iss. 2 (2021), s.189-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/pathogens10020189
- Verified by:
- Gdańsk University of Technology
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