Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion
Аутори
Stanković, MiaKljun, Jakob
Stevanović, Nevena Lj.
Lazić, Jelena
Škaro Bogojević, Sanja
Vojnović, Sandra
Zlatar, Matija
Nikodinović-Runić, Jasmina
Turel, Iztok
Đuran, Miloš
Glišić, Biljana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms... in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied.
Кључне речи:
silver(I) complexes / azoles / econazole / voriconazole / clotrimazole / synthesis / characterization / antimicrobial properties / single-crystal X-ray diffraction / coordination / DFT calculationsИзвор:
Dalton Transactions, 2024Издавач:
- Royal Society of Chemistry (RSC)
Финансирање / пројекти:
- Serbian Academy of Sciences and Arts (F128)
- European Cooperation in Science and Technology (CA21145 - COST Action EURESTOP)
- TMMagCat - Tailoring Molecular Magnets and Catalysts Based on Transition Metal Complexes (RS-ScienceFundRS-Ideje-7750288)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200122 (Универзитет у Крагујевцу, Природно-математички факултет) (RS-MESTD-inst-2020-200122)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
- Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja - Bilateral project No. 19 between University of Kragujevac, Faculty of Science, Serbia and University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia
- Javna Agencija za Raziskovalno Dejavnost RS (I0-0022)
- Javna Agencija za Raziskovalno Dejavnost RS ( P1-0175)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Stanković, Mia AU - Kljun, Jakob AU - Stevanović, Nevena Lj. AU - Lazić, Jelena AU - Škaro Bogojević, Sanja AU - Vojnović, Sandra AU - Zlatar, Matija AU - Nikodinović-Runić, Jasmina AU - Turel, Iztok AU - Đuran, Miloš AU - Glišić, Biljana PY - 2024 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2303 AB - Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied. PB - Royal Society of Chemistry (RSC) T2 - Dalton Transactions T1 - Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion DO - 10.1039/D3DT03010E ER -
@article{ author = "Stanković, Mia and Kljun, Jakob and Stevanović, Nevena Lj. and Lazić, Jelena and Škaro Bogojević, Sanja and Vojnović, Sandra and Zlatar, Matija and Nikodinović-Runić, Jasmina and Turel, Iztok and Đuran, Miloš and Glišić, Biljana", year = "2024", abstract = "Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied.", publisher = "Royal Society of Chemistry (RSC)", journal = "Dalton Transactions", title = "Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion", doi = "10.1039/D3DT03010E" }
Stanković, M., Kljun, J., Stevanović, N. Lj., Lazić, J., Škaro Bogojević, S., Vojnović, S., Zlatar, M., Nikodinović-Runić, J., Turel, I., Đuran, M.,& Glišić, B.. (2024). Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion. in Dalton Transactions Royal Society of Chemistry (RSC).. https://doi.org/10.1039/D3DT03010E
Stanković M, Kljun J, Stevanović NL, Lazić J, Škaro Bogojević S, Vojnović S, Zlatar M, Nikodinović-Runić J, Turel I, Đuran M, Glišić B. Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion. in Dalton Transactions. 2024;. doi:10.1039/D3DT03010E .
Stanković, Mia, Kljun, Jakob, Stevanović, Nevena Lj., Lazić, Jelena, Škaro Bogojević, Sanja, Vojnović, Sandra, Zlatar, Matija, Nikodinović-Runić, Jasmina, Turel, Iztok, Đuran, Miloš, Glišić, Biljana, "Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion" in Dalton Transactions (2024), https://doi.org/10.1039/D3DT03010E . .