Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
Authors
Stevanović, Nevena Lj.Aleksić, Ivana
Kljun, Jakob
Škaro Bogojević, Sanja
Veselinović, Aleksandar
Nikodinović-Runić, Jasmina
Turel, Iztok
Djuran, Milos
Glišić, Biljana
Article (Published version)
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Show full item recordAbstract
Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl2(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl2(fcz)(2)]Greek ano teleia2C(2)H(5)OH}(n), 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex 2 showed significantly higher antifungal activity against Candida krusei and Candida parapsilosis. All tested compounds reduced the total amount of ergosterol at subinhibitory concentrations, indicating that the mode of activity of fluconazole was retained within the complexes, which was corroborated via molecular docking with cytochrome P450 sterol 14 alpha-demethylase (CYP51) as a target. Electrostatic, steric and internal energy interactions between the complexes and enzyme showed that 2 has higher binding potency to this target. Both comp...lexes showed strong inhibition of C. albicans filamentation and biofilm formation at subinhibitory concentrations, with 2 being able to reduce the adherence of C. albicans to A549 cells in vitro. Complex 2 was able to reduce pyocyanin production in Pseudomonas aeruginosa between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex 2 may be further examined in the mixed Candida-P. aeruginosa infections.
Keywords:
zinc(II) complex / fluconazole / copper(II) complex / antifungal agents / anti-biofilm activitySource:
Pharmaceuticals, 2021, 14, 1Publisher:
- MDPI, Basel
Funding / projects:
- Slovenian Research Agency [P1-0175]
- Serbian Academy of Sciences and Arts [01-2019-F65, F128]
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200122 (University of Kragujevac, Faculty of Science) (RS-MESTD-inst-2020-200122)
DOI: 10.3390/ph14010024
ISSN: 1424-8247
WoS: 000610719200001
Scopus: 2-s2.0-85098861613
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Stevanović, Nevena Lj. AU - Aleksić, Ivana AU - Kljun, Jakob AU - Škaro Bogojević, Sanja AU - Veselinović, Aleksandar AU - Nikodinović-Runić, Jasmina AU - Turel, Iztok AU - Djuran, Milos AU - Glišić, Biljana PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1484 AB - Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl2(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl2(fcz)(2)]Greek ano teleia2C(2)H(5)OH}(n), 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex 2 showed significantly higher antifungal activity against Candida krusei and Candida parapsilosis. All tested compounds reduced the total amount of ergosterol at subinhibitory concentrations, indicating that the mode of activity of fluconazole was retained within the complexes, which was corroborated via molecular docking with cytochrome P450 sterol 14 alpha-demethylase (CYP51) as a target. Electrostatic, steric and internal energy interactions between the complexes and enzyme showed that 2 has higher binding potency to this target. Both complexes showed strong inhibition of C. albicans filamentation and biofilm formation at subinhibitory concentrations, with 2 being able to reduce the adherence of C. albicans to A549 cells in vitro. Complex 2 was able to reduce pyocyanin production in Pseudomonas aeruginosa between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex 2 may be further examined in the mixed Candida-P. aeruginosa infections. PB - MDPI, Basel T2 - Pharmaceuticals T1 - Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential IS - 1 VL - 14 DO - 10.3390/ph14010024 ER -
@article{ author = "Stevanović, Nevena Lj. and Aleksić, Ivana and Kljun, Jakob and Škaro Bogojević, Sanja and Veselinović, Aleksandar and Nikodinović-Runić, Jasmina and Turel, Iztok and Djuran, Milos and Glišić, Biljana", year = "2021", abstract = "Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl2(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl2(fcz)(2)]Greek ano teleia2C(2)H(5)OH}(n), 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex 2 showed significantly higher antifungal activity against Candida krusei and Candida parapsilosis. All tested compounds reduced the total amount of ergosterol at subinhibitory concentrations, indicating that the mode of activity of fluconazole was retained within the complexes, which was corroborated via molecular docking with cytochrome P450 sterol 14 alpha-demethylase (CYP51) as a target. Electrostatic, steric and internal energy interactions between the complexes and enzyme showed that 2 has higher binding potency to this target. Both complexes showed strong inhibition of C. albicans filamentation and biofilm formation at subinhibitory concentrations, with 2 being able to reduce the adherence of C. albicans to A549 cells in vitro. Complex 2 was able to reduce pyocyanin production in Pseudomonas aeruginosa between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex 2 may be further examined in the mixed Candida-P. aeruginosa infections.", publisher = "MDPI, Basel", journal = "Pharmaceuticals", title = "Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential", number = "1", volume = "14", doi = "10.3390/ph14010024" }
Stevanović, N. Lj., Aleksić, I., Kljun, J., Škaro Bogojević, S., Veselinović, A., Nikodinović-Runić, J., Turel, I., Djuran, M.,& Glišić, B.. (2021). Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential. in Pharmaceuticals MDPI, Basel., 14(1). https://doi.org/10.3390/ph14010024
Stevanović NL, Aleksić I, Kljun J, Škaro Bogojević S, Veselinović A, Nikodinović-Runić J, Turel I, Djuran M, Glišić B. Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential. in Pharmaceuticals. 2021;14(1). doi:10.3390/ph14010024 .
Stevanović, Nevena Lj., Aleksić, Ivana, Kljun, Jakob, Škaro Bogojević, Sanja, Veselinović, Aleksandar, Nikodinović-Runić, Jasmina, Turel, Iztok, Djuran, Milos , Glišić, Biljana, "Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential" in Pharmaceuticals, 14, no. 1 (2021), https://doi.org/10.3390/ph14010024 . .