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The Effect of Conjugation with Octaarginine, a Cell-Penetrating Peptide on Antifungal Activity of Imidazoacridinone Derivative
Abstract
Acridine cell-penetrating peptide conjugates are an extremely important family of compounds in antitumor chemotherapy. These conjugates are not so widely analysed in antimicrobial therapy, although bioactive peptides could be used as nanocarriers to smuggle antimicrobial compounds. An octaarginine conjugate of an imidazoacridinone derivative (Compound 1-R8) synthetized by us exhibited high antifungal activity against reference and fluconazole-resistant clinical strains (MICs ≤ 4 μg mL−1). Our results clearly demonstrate the qualitative difference in accumulation of the mother compound and Compound 1-R8 conjugate into fungal cells. Only the latter was transported and accumulated effectively. Microscopic and flow cytometry analysis provide some evidence that the killing activity of Compound 1-R8 may be associated with a change in the permeability of the fungal cell membrane. The conjugate exhibited low cytotoxicity against human embryonic kidney (HEK-293) and human liver (HEPG2) cancer cell lines. Nevertheless, the selectivity index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted in a high antifungal effect.
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Authors (7)
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Damian Neubauer
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Wojciech Kamysz dr hab
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- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms222413190
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 22,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Rząd K., Paluszkiewicz E., Neubauer D., Olszewski M., Kozłowska-Tylingo K., Kamysz W., Gabriel I.: The Effect of Conjugation with Octaarginine, a Cell-Penetrating Peptide on Antifungal Activity of Imidazoacridinone Derivative// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -,iss. 22(24) (2021),
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms222413190
- Sources of funding:
-
- IDUB
- Verified by:
- Gdańsk University of Technology
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