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<sub>2</sub>(fcz)<sub>2</sub>]<sup>.</sup>5H<sub>2</sub>O}<sub>n</sub>, <b>1</b>, and {[ZnCl<sub>2</sub>(fcz)<sub>...
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/1/24 |
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| author | Nevena Lj. Stevanović Ivana Aleksic Jakob Kljun Sanja Skaro Bogojevic Aleksandar Veselinovic Jasmina Nikodinovic-Runic Iztok Turel Miloš I. Djuran Biljana Đ. Glišić |
| author_facet | Nevena Lj. Stevanović Ivana Aleksic Jakob Kljun Sanja Skaro Bogojevic Aleksandar Veselinovic Jasmina Nikodinovic-Runic Iztok Turel Miloš I. Djuran Biljana Đ. Glišić |
| author_sort | Nevena Lj. Stevanović |
| collection | DOAJ |
| description | Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl<sub>2</sub>(fcz)<sub>2</sub>]<sup>.</sup>5H<sub>2</sub>O}<sub>n</sub>, <b>1</b>, and {[ZnCl<sub>2</sub>(fcz)<sub>2</sub>]·2C<sub>2</sub>H<sub>5</sub>OH}<sub>n</sub>, <b>2</b>, 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 <b>2</b> showed significantly higher antifungal activity against <i>Candida krusei</i> and <i>Candida parapsilosis</i>. 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 <b>2</b> has higher binding potency to this target. Both complexes showed strong inhibition of <i>C. albicans</i> filamentation and biofilm formation at subinhibitory concentrations, with <b>2</b> being able to reduce the adherence of <i>C. albicans</i> to A549 cells in vitro. Complex <b>2</b> was able to reduce pyocyanin production in <i>Pseudomonas aeruginosa</i> between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex <b>2</b> may be further examined in the mixed <i>Candida-P. aeruginosa</i> infections. |
| first_indexed | 2024-03-10T13:40:36Z |
| format | Article |
| id | doaj.art-5bd7f3437fa343d3b66391985e05f2c3 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T13:40:36Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-5bd7f3437fa343d3b66391985e05f2c32023-11-21T03:05:12ZengMDPI AGPharmaceuticals1424-82472020-12-011412410.3390/ph14010024Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic PotentialNevena Lj. Stevanović0Ivana Aleksic1Jakob Kljun2Sanja Skaro Bogojevic3Aleksandar Veselinovic4Jasmina Nikodinovic-Runic5Iztok Turel6Miloš I. Djuran7Biljana Đ. Glišić8Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, SerbiaFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, SloveniaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, SerbiaDepartment of Chemistry, Faculty of Medicine, University of Niš, Blvd. Dr Zorana Djindjica 81, 18108 Niš, SerbiaInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, SerbiaFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, SloveniaDepartment of Chemical and Biological Sciences, Serbian Academy of Sciences and Arts, Knez Mihailova 35, 11000 Belgrade, SerbiaDepartment of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, SerbiaCopper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl<sub>2</sub>(fcz)<sub>2</sub>]<sup>.</sup>5H<sub>2</sub>O}<sub>n</sub>, <b>1</b>, and {[ZnCl<sub>2</sub>(fcz)<sub>2</sub>]·2C<sub>2</sub>H<sub>5</sub>OH}<sub>n</sub>, <b>2</b>, 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 <b>2</b> showed significantly higher antifungal activity against <i>Candida krusei</i> and <i>Candida parapsilosis</i>. 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 <b>2</b> has higher binding potency to this target. Both complexes showed strong inhibition of <i>C. albicans</i> filamentation and biofilm formation at subinhibitory concentrations, with <b>2</b> being able to reduce the adherence of <i>C. albicans</i> to A549 cells in vitro. Complex <b>2</b> was able to reduce pyocyanin production in <i>Pseudomonas aeruginosa</i> between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex <b>2</b> may be further examined in the mixed <i>Candida-P. aeruginosa</i> infections.https://www.mdpi.com/1424-8247/14/1/24copper(II) complexzinc(II) complexfluconazoleantifungal agentsanti-biofilm activity |
| spellingShingle | Nevena Lj. Stevanović Ivana Aleksic Jakob Kljun Sanja Skaro Bogojevic Aleksandar Veselinovic Jasmina Nikodinovic-Runic Iztok Turel Miloš I. Djuran Biljana Đ. Glišić Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential Pharmaceuticals copper(II) complex zinc(II) complex fluconazole antifungal agents anti-biofilm activity |
| 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 | copper(II) complex zinc(II) complex fluconazole antifungal agents anti-biofilm activity |
| url | https://www.mdpi.com/1424-8247/14/1/24 |
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