Mia Stanković (Avtor), Sanja Skaro-Bogojevic (Avtor), Jakob Kljun (Avtor), Žiko Milanović (Avtor), Nevena Lj. Stevanović (Avtor), Jelena Lazić (Avtor), Sandra Vojnović (Avtor), Iztok Turel (Avtor), Miloš I. Djuran (Avtor), Biljana Đ. Glišić (Avtor)

Povzetek

Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV–Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(H$_2$O)]CH$_3$SO$_3$}$_n$ (1), {[Ag(vcz)$_2$]BF$_4$}$_n$ (2) and {[Ag(vcz)$_2$]PF$_6$}$_n$ (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry. On the other hand, DFT calculations revealed that the investigated silver(I) complexes 1–3 in DMSO exist as linear [Ag(vcz-N2)(vcz-N19)]$^+$ (1a), [Ag(vcz-N2)(vcz-N4)]$^+$ (2a) and [Ag(vcz-N4)$_2]^+$ (3a) species, respectively. The evaluated complexes showed an enhanced anti-Candida activity compared to the parent drug with minimal inhibitory concentration (MIC) values in the range of 0.02–1.05 μM. In comparison with vcz, the corresponding silver(I) complexes showed better activity in prevention hyphae and biofilm formation of C. albicans, indicating that they could be considered as promising agents against Candida that significantly inhibit its virulence. Also, these complexes are much better inhibitors of ergosterol synthesis in the cell membrane of C. albicans at the concentration of 0.5 × MIC. This is also confirmed by a molecular docking, which revealed that complexes 1a – 3a showed better inhibitory activity than vcz against the sterol 14α-demethylase enzyme cytochrome P450 (CYP51B), which plays a crucial role in the formation of ergosterol.

Ključne besede

srebrovi(I) kompleksi;vorikonazol;koordinacijski polimeri;kalkulacije DFT;proti Candidna aktivnost;CYP51B;silver(I) complexes;Voriconazole;coordination polymers;DFT calculations;anti-Candida activity;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FKKT - Fakulteta za kemijo in kemijsko tehnologijo
UDK: 546.571
COBISS: 194720259 Povezava se bo odprla v novem oknu
ISSN: 0162-0134
Št. ogledov: 93
Št. prenosov: 31
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: srebrovi(I) kompleksi;vorikonazol;koordinacijski polimeri;kalkulacije DFT;protikandidna aktivnost;CYP51B;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-13
Zvezek: ǂVol. ǂ256, [article no.] 112572
Čas izdaje: Jul. 2024
DOI: 10.1016/j.jinorgbio.2024.112572
ID: 23636636