Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
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 which are highly effective in some cases, however, they have limitations in usage: Nephrotoxi...
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doaj-c6acd40ef8854a9da44a5cac9144dc382021-02-10T00:05:50ZengMDPI AGPathogens2076-08172021-02-011018918910.3390/pathogens10020189Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II ActivityIwona Gabriel0Kamila Rząd1Ewa Paluszkiewicz2Katarzyna Kozłowska-Tylingo3Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, 80-233 Gdańsk, PolandIn 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 which are 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 Capridine β antifungal activity depends on the kind of strains analyzed (MICs range 0.5–64 μg mL<sup>−1</sup>) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus <i>Candida albicans</i> was performed. IE1 exhibited no activity against fungal cells due to an inability to enter the cells. 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 β only slightly diminished the catalytic activity of yTOPOII.https://www.mdpi.com/2076-0817/10/2/189<i>Candida albicans</i>acridineantifungaltopoisomeraseinhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Iwona Gabriel Kamila Rząd Ewa Paluszkiewicz Katarzyna Kozłowska-Tylingo |
spellingShingle |
Iwona Gabriel Kamila Rząd Ewa Paluszkiewicz Katarzyna Kozłowska-Tylingo Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity Pathogens <i>Candida albicans</i> acridine antifungal topoisomerase inhibitor |
author_facet |
Iwona Gabriel Kamila Rząd Ewa Paluszkiewicz Katarzyna Kozłowska-Tylingo |
author_sort |
Iwona Gabriel |
title |
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity |
title_short |
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity |
title_full |
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity |
title_fullStr |
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity |
title_full_unstemmed |
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity |
title_sort |
antifungal activity of capridine β as a consequence of its biotransformation into metabolite affecting yeast topoisomerase ii activity |
publisher |
MDPI AG |
series |
Pathogens |
issn |
2076-0817 |
publishDate |
2021-02-01 |
description |
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 which are 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 Capridine β antifungal activity depends on the kind of strains analyzed (MICs range 0.5–64 μg mL<sup>−1</sup>) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus <i>Candida albicans</i> was performed. IE1 exhibited no activity against fungal cells due to an inability to enter the cells. 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 β only slightly diminished the catalytic activity of yTOPOII. |
topic |
<i>Candida albicans</i> acridine antifungal topoisomerase inhibitor |
url |
https://www.mdpi.com/2076-0817/10/2/189 |
work_keys_str_mv |
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