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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?(thiouracil) (Complex 1) and Cu(Bipy)Cl?(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.

SUBMITTER: Gomes da Silva Dantas F

PROVIDER: S-EPMC6222317 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Gomes da Silva Dantas Fabiana F Araújo de Almeida-Apolonio Adriana A Pires de Araújo Renata R Regiane Vizolli Favarin Lis L Fukuda de Castilho Pamella P de Oliveira Galvão Fernanda F Inez Estivalet Svidzinski Terezinha T Antônio Casagrande Gleison G Mari Pires de Oliveira Kelly K

Molecules (Basel, Switzerland) 20180726 8

The high mortality rate of candidemia and the limited option for the treatment of <i>Candida</i> 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 <i>Candida</i>. The complexe ...[more]

PMID: 30049937

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Project description:Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii, which form the C. haemulonii complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti-Candida potential of metal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of C. haemulonii species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of each C. haemulonii species complex were used and the effect of the metal chelates on viability was determined utilizing the CLSI standard protocol and on biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was evaluated by the MTT assay, employing lung epithelial cells. The majority of the metal chelates were capable of interfering with the viability of planktonic-growing cells of all the fungal isolates. The silver complexes were the most effective drugs (overall geometric mean of the minimum inhibitory concentration (GM-MIC) ranged from 0.26 to 2.16 ?M), followed by the manganese (overall GM-MIC ranged from 0.87 to 10.71 ?M) and copper (overall GM-MIC ranged from 3.37 to >72 ?M) chelates. The manganese chelates (CC50 values ranged from 234.51 to >512 ?M) were the least toxic to the mammalian cells, followed by the silver (CC50 values ranged from 2.07 to 13.63 ?M) and copper (CC50 values ranged from 0.53 to 3.86 ?M) compounds. When tested against mature biofilms, the chelates were less active, with MICs ranging from 2- to 33-fold higher levels when compared to the planktonic MIC counterparts. Importantly, manganese(II), copper(II), and silver(I) phen chelates are relatively cheap and easy to synthesize and they offer significant antifungal chemotherapeutic potential for the treatment of highly resistant pathogens.

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Dataset Information

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

Publications

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

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