Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity - Publikacja - MOST Wiedzy

Wyszukiwarka

Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity

Abstrakt

Fungal pathogens are considered as serious factors for deadly diseases and are a case of medical concern. Invasive fungal infections also complicate the clinical course of COVID-19, leading to a significant increase in mortality. Furthermore, fungal strains' multidrug resistance has increased the demand for antifungals with a different mechanism of action. The present study aimed to identify antifungal compounds targeting yeast topoisomerase II (yTOPOII) derived from well-known human topoisomerase II (hTOPOII) poisons C-1305 and C-1311. Two sets of derivatives: triazoloacridinones (IKE1-8) and imidazoacridinones (IKE9-14) were synthetized and evaluated with a specific emphasis on the molecular mechanism of action. Our results indicated that their effectiveness as enzyme inhibitors was not solely due to intercalation ability but also as a result of influence on catalytic activity by the formation of covalent complexes between plasmid DNA and yTOPOII. Lysine conjunction increased the strength of the compound's interaction with DNA and improved penetration into the fungal cells. Triazoloacridinone derivatives in contrast to starting compound C-1305 exhibited moderate antifungal activity and at least twice lower cytotoxicity. Importantly, compounds (IKE5-8) were not substrates for multidrug ABC transporters whereas a derivative conjugated with lysine (IKE7), showed the ability to overcome C. glabrata fluconazole-resistance (MIC 32–64 µg mL−1).

Cytowania

  • 1

    CrossRef

  • 0

    Web of Science

  • 1

    Scopus

Słowa kluczowe

Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
Scientific Reports nr 14,
ISSN: 2045-2322
Język:
angielski
Rok wydania:
2024
Opis bibliograficzny:
Rząd K., Gabriel I., Paluszkiewicz E., Kuplińska A., Olszewski M., Chylewska A., Dąbrowska A. M., Kozłowska-Tylingo K.: Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity// Scientific Reports -Vol. 14, (2024), s.3594-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1038/s41598-024-54252-0
Źródła finansowania:
  • IDUB
Weryfikacja:
Politechnika Gdańska

wyświetlono 78 razy

Publikacje, które mogą cię zainteresować

Meta Tagi