A Promising Copper(II) Complex as Antifungal and Antibiofilm Drug against Yeast Infection

Abstract

The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl ₂(thiouracil) (Complex 1) and Cu(Bipy)Cl ₂(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti- Candida therapy.