Silver(I) complexes with voriconazole as promising anti-Candida agents

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Mycology

Background:

• Metal ions can modify drug properties.
• Voriconazole (vcz) is an antifungal agent.
• Developing novel antimycotics is crucial for combating fungal infections.

Purpose of the Study:

• To synthesize and characterize silver(I) complexes with voriconazole (vcz).
• To evaluate the antimycotic activity of these novel complexes against Candida species.
• To investigate the mechanism of action of the silver(I)-vcz complexes.

Main Methods:

• Synthesis of silver(I) complexes with vcz.
• Characterization using mass spectrometry, IR, UV-Vis, NMR, and single-crystal X-ray diffraction.
• Antifungal activity testing (MIC values), hyphae and biofilm inhibition assays, ergosterol synthesis inhibition assays, and molecular docking studies.

Main Results:

• Three polymeric silver(I)-vcz complexes with distorted tetrahedral geometry were synthesized.
• DFT calculations indicated linear species in DMSO.
• The silver(I) complexes exhibited enhanced anti-Candida activity, reduced MIC values, and superior inhibition of hyphae, biofilm formation, and ergosterol synthesis compared to vcz.
• Molecular docking confirmed better inhibition of CYP51B by the complexes.

Conclusions:

• Silver(I) complexes of voriconazole are effective antimycotic agents with improved activity over the parent drug.
• These complexes show potential in inhibiting Candida virulence factors and ergosterol biosynthesis.
• The developed silver(I)-vcz complexes represent promising candidates for new antifungal therapies.