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

被引:42
作者
da Silva Dantas, Fabiana Gomes [1 ]
de Almeida-Apolonio, Adriana Araujo [2 ]
de Araujo, Renata Pires [3 ]
Vizolli Favarin, Lis Regiane [4 ]
de Castilho, Pamella Fukuda [1 ]
Galvao, Fernanda de Oliveira [1 ]
Estivalet Svidzinski, Terezinha Inez [5 ]
Casagrande, Gleison Antonio [4 ]
Pires de Oliveira, Kelly Mari [1 ,6 ]
机构
[1] Fed Univ Grande Dourados, Fac Hlth Sci, BR-79804970 Dourados, MS, Brazil
[2] Univ Fed Mato Grosso do Sul, Fac Med, BR-79070900 Campo Grande, MS, Brazil
[3] Fed Univ Grande Dourados, Fac Exact Sci & Technol, BR-79804970 Dourados, MS, Brazil
[4] Univ Fed Mato Grosso do Sul, Inst Chem, BR-79074460 Campo Grande, MS, Brazil
[5] Univ Estadual Maringa, Dept Clin Anal & Biomed, BR-87020900 Maringa, PR, Brazil
[6] Fed Univ Grande Dourados, Fac Biol & Environm Sci, BR-79804970 Dourados, MS, Brazil
关键词
antifungal; ames test; biofilm; copper(II); 2-thiouracil; STRUCTURAL-CHARACTERIZATION; PYRAZOLINE LIGANDS; FUNGAL-INFECTIONS; PATHOGENICITY; 2-THIOURACIL; CANDIDIASIS; MECHANISMS; REDUCTION; BRAZIL; MODE;
D O I
10.3390/molecules23081856
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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.
引用
收藏
页数:14
相关论文
共 48 条
[1]  
Adelaide 0.M., 2013, J. Chem. Pharm. Res, V5, P69
[2]   A novel series of thiazolyl-pyrazoline derivatives: Synthesis and evaluation of antifungal activity, cytotoxicity and genotoxicity [J].
Altintop, Mehlika Dilek ;
Ozdemir, Ahmet ;
Turan-Zitouni, Gulhan ;
Ilgm, Sinem ;
Atli, Ozlem ;
Demirel, Rasime ;
Kaplancikli, Zafer Asim .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 92 :342-352
[3]   Portrait of Candida Species Biofilm Regulatory Network Genes [J].
Araujo, Daniela ;
Henriques, Mariana ;
Silva, Sonia .
TRENDS IN MICROBIOLOGY, 2017, 25 (01) :62-75
[4]   AN EMPIRICAL-APPROACH TO THE STATISTICAL-ANALYSIS OF MUTAGENESIS DATA FROM THE SALMONELLA TEST [J].
BERNSTEIN, L ;
KALDOR, J ;
MCCANN, J ;
PIKE, MC .
MUTATION RESEARCH, 1982, 97 (04) :267-281
[5]   Candida Biofilms: Development, Architecture, and Resistance [J].
Chandra, Jyotsna ;
Mukherjee, Pranab K. .
MICROBIOLOGY SPECTRUM, 2015, 3 (04)
[6]   Candida biofilms associated with CVC and medical devices [J].
Chandra, Jyotsna ;
Mukherjee, Pranab K. ;
Ghannoum, Mahmoud A. .
MYCOSES, 2012, 55 :46-57
[7]  
Clinical and laboratory Standards Institute (CLSI), 2008, REF METH BROTH DIL A
[8]   Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives [J].
De Monte, Celeste ;
Carradori, Simone ;
Bizzarri, Bruna ;
Bolasco, Adriana ;
Caprara, Federica ;
Mollica, Adriano ;
Rivanera, Daniela ;
Mari, Emanuela ;
Zicari, Alessandra ;
Akdemir, Atilla ;
Secci, Daniela .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2016, 107 :82-96
[9]   Fungal Biofilms, Drug Resistance, and Recurrent Infection [J].
Desai, Jigar V. ;
Mitchell, Aaron P. ;
Andes, David R. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2014, 4 (10)
[10]   Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program [J].
Doi, Andre Mario ;
Campos Pignatari, Antonio Carlos ;
Edmond, Michael B. ;
Marra, Alexandre Rodrigues ;
Aranha Camargo, Luis Fernando ;
Siqueira, Ricardo Andreotti ;
da Mota, Vivian Pereira ;
Colombo, Arnaldo Lopes .
PLOS ONE, 2016, 11 (01)