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)Cl2(thiouracil) (Complex 1) and Cu(Bipy)Cl2(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.

Multifunctional Copper-Containing Mesoporous Glass Nanoparticles as Antibacterial and Proangiogenic Agents for Chronic Wounds

“…Whilst there is some evidence that bacteria can develop resistance mechanisms to certain forms of copper and silver (Percival et al, 2005;Santo et al, 2011;Finley et al, 2015;Hobman and Crossman, 2015;Williams et al, 2016), they are still promising as antimicrobials due to their broad ranges of biocidal activity against multiple microorganisms, including both Gram positive and Gram negative bacteria. Evidence also exists that metal ions such as silver and copper are either directly antifungal or enhance the actions of antifungal agents (Gomes da Silva Dantas et al, 2018;Radhakrishnan et al, 2018).…”

Synthesis, Structural Characterization and Antimicrobial Evaluation of Ruthenium Complexes with Heteroaromatic Carboxylic Acids

“…Biologically active metal complexes have gained special significance due to the need for the prevention of resistance of bacterial strains. Recently, several Cu(II), Ga(III), Zn(II), Mn(II), Ag(I), Au(III) and Ru(II) complexes with bioactive ligands have been tested as potential antibiofilm and antimicrobial agents . Among above mentioned metal complexes, ruthenium compounds are promising for medicinal and biotechnological applications as they present unique properties: (i) multiple oxidation states (II, III and IV), which are accessible in physiological conditions; (ii) favorable ligand‐exchange kinetics; (iii) multiple cytotoxic routes involving the competing processes of extracellular protein binding (active transport), due to the ability to mimic iron and cellular uptake (passive diffusion); (iv) different molecular pathways involving the concurrent intercalation and covalent binding with DNA and binding to extracellular sites inducing conformational modifications; (v) numerous synthetic opportunities for modifying the biological activity which depends on both the oxidation state of the metal center and the associated ligands surrounding it.…”

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

“…Indeed, the anti-biofilm activity of fluconazole has been previously reported on C. glabrata, C. parapsilosis and C. rugosa biofilms, with fluconazole causing significant damage to the vitality and integrity of Candida cells [ 49 ]. In addition, Gomes da Silva Dantas et al demonstrating the inhibition of 9.9% of the C. glabrata and C. krusei biofilms by copper(II) complex with 2-thiouracil [ 50 ].…”