20.500.12556/RUL-156101 Silver(I) complexes with voriconazole as promising anti-Candida agents 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. silver(I) complexes voriconazole coordination polymers DFT calculations anti-Candida activity CYP51B srebrovi(I) kompleksi vorikonazol koordinacijski polimeri kalkulacije DFT protikandidna aktivnost CYP51B true false true Angleški jezik Slovenski jezik Članek v reviji 2024-05-08 10:13:09 2024-05-08 10:13:11 2024-05-23 10:29:28 0000-00-00 00:00:00 2024 0 0 13 str. Vol. 256, art. 112572 Jul. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 546.571 0162-0134 10.1016/j.jinorgbio.2024.112572 194720259 1-s2.0-S0162013424000953-main.pdf 1-s2.0-S0162013424000953-main.pdf 1 342C0CF170E04668E36B7E94F8BFDA3F 4d42b5a2885f60b54f8bfa0dc414260b37e36b2df1ecb5a5b673c9d4def2bd84 9db4ae82-0d14-11ef-a389-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183342 https://www.sciencedirect.com/science/article/pii/S0162013424000953 1 d02d4222-0d12-11ef-a389-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183340 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0