Search
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.
Citations
-
7
CrossRef
-
0
Web of Science
-
8
Scopus
Authors (7)
-
Damian Neubauer
-
Wojciech Kamysz dr hab
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms222413190
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
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
seen 156 times
Recommended for you
Peptide dendrimers as antifungal agents and carriers for potential antifungal agent—N3‐(4‐methoxyfumaroyl)‐(S)‐2,3‐ diaminopropanoic acid—synthesis and antimicrobial activity
- M. Stolarska,
- K. Gucwa,
- Z. Urbańczyk-Lipkowska
- + 1 authors
New Peptide Based Fluconazole Conjugates with Expanded Molecular Targets
- W. Brankiewicz,
- J. Okońska,
- K. Serbakowska
- + 6 authors
Xanthone synthetic derivatives with high anticandidal activity and positive mycostatic selectivity index values
- K. Rząd,
- R. Ioannidi,
- P. Marakos
- + 4 authors
Conjugates of Ciprofloxacin and Levofloxacin with Cell-Penetrating Peptide Exhibit Antifungal Activity and Mammalian Cytotoxicity
- N. Ptaszyńska,
- K. Gucwa,
- K. Olkiewicz
- + 10 authors