Copper(II) and zinc(II) complexes with the clinically used fluconazole : comparison of antifungal activity and therapeutic potential

Stevanović, Nevena Lj. (author), Aleksić, Ivana (author), Kljun, Jakob (author), Skaro-Bogojevic, Sanja (author), Veselinovic, Aleksandar (author), Nikodinović-Runić, Jasmina (author), Turel, Iztok (author), Djuran, Miloš I. (author), Glišić, Biljana Đ. (author)

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.

• Language: English
• Keywords: copper(II) complex, zinc(II) complex, fluconazole, antifungal agents, anti-biofilm activity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 20 str.
• Numbering: Vol. 14, iss. 1, art. 24
• PID: 20.500.12556/RUL-134922
• UDC: 546.47:546.562
• ISSN on article: 1424-8247
• DOI: 10.3390/ph14010024
• COBISS.SI-ID: 45141251
• Publication date in RUL: 11.02.2022

Record is a part of a journal

• Title: Pharmaceuticals
• Shortened title: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.01.2021

Secondary language

• Language: Slovenian
• Keywords: baker, cink, kovinski kompleksi