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.
Autorzy
- dr inż. Kamila Rząd link otwiera się w nowej karcie ,
- dr inż. Ewa Paluszkiewicz link otwiera się w nowej karcie ,
- Damian Neubauer,
- mgr Mateusz Olszewski link otwiera się w nowej karcie ,
- dr inż. Katarzyna Kozłowska-Tylingo link otwiera się w nowej karcie ,
- dr hab Wojciech Kamysz,
- dr hab. inż. Iwona Gabriel link otwiera się w nowej karcie
Informacje dodatkowe
- DOI
- Cyfrowy identyfikator dokumentu elektronicznego link otwiera się w nowej karcie 10.3390/ijms222413190
- Kategoria
- Publikacja w czasopiśmie
- Typ
- artykuły w czasopismach
- Język
- angielski
- Rok wydania
- 2021