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Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential

Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl(2)(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl(2)(fcz)(2)]·2C(2)H(5)OH}(n), 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises f...

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Autores principales: Stevanović, Nevena Lj., Aleksic, Ivana, Kljun, Jakob, Skaro Bogojevic, Sanja, Veselinovic, Aleksandar, Nikodinovic-Runic, Jasmina, Turel, Iztok, Djuran, Miloš I., Glišić, Biljana Đ.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823955/
https://www.ncbi.nlm.nih.gov/pubmed/33396681
http://dx.doi.org/10.3390/ph14010024
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author Stevanović, Nevena Lj.
Aleksic, Ivana
Kljun, Jakob
Skaro Bogojevic, Sanja
Veselinovic, Aleksandar
Nikodinovic-Runic, Jasmina
Turel, Iztok
Djuran, Miloš I.
Glišić, Biljana Đ.
author_facet Stevanović, Nevena Lj.
Aleksic, Ivana
Kljun, Jakob
Skaro Bogojevic, Sanja
Veselinovic, Aleksandar
Nikodinovic-Runic, Jasmina
Turel, Iztok
Djuran, Miloš I.
Glišić, Biljana Đ.
author_sort Stevanović, Nevena Lj.
collection PubMed
description Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl(2)(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl(2)(fcz)(2)]·2C(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 14α-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.
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spelling pubmed-78239552021-01-24 Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential Stevanović, Nevena Lj. Aleksic, Ivana Kljun, Jakob Skaro Bogojevic, Sanja Veselinovic, Aleksandar Nikodinovic-Runic, Jasmina Turel, Iztok Djuran, Miloš I. Glišić, Biljana Đ. Pharmaceuticals (Basel) Article Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl(2)(fcz)(2)](.)5H(2)O}(n), 1, and {[ZnCl(2)(fcz)(2)]·2C(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 14α-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. MDPI 2020-12-30 /pmc/articles/PMC7823955/ /pubmed/33396681 http://dx.doi.org/10.3390/ph14010024 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stevanović, Nevena Lj.
Aleksic, Ivana
Kljun, Jakob
Skaro Bogojevic, Sanja
Veselinovic, Aleksandar
Nikodinovic-Runic, Jasmina
Turel, Iztok
Djuran, Miloš I.
Glišić, Biljana Đ.
Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title_full Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title_fullStr Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title_full_unstemmed Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title_short Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
title_sort copper(ii) and zinc(ii) complexes with the clinically used fluconazole: comparison of antifungal activity and therapeutic potential
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823955/
https://www.ncbi.nlm.nih.gov/pubmed/33396681
http://dx.doi.org/10.3390/ph14010024
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