de Sá Nívea P, Pôssa Ana P, Perez Pilar, Ferreira Jaqueline M S, Fonseca Nayara C, Lino Cleudiomar I, Cruz Lana B, de Oliveira Renata B, Rosa Carlos A, Borelli Beatriz M, Mylonakis Eleftherios, Fuchs Beth B, Johann Susana
Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Antonio Carlos, 6627, Pampulha - CEP 31270-901, Belo Horizonte - MG, Brazil.
Laboratorio de Microbiologia, Campus Centro- Oeste Dona Lindu, Universidade Federal de Sao Joao del-Rei, Divinópolis, Minas Gerais, Brazil.
Infect Disord Drug Targets. 2019;19(4):428-438. doi: 10.2174/1871526518666180531101605.
The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds.
To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans.
The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans.
CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase.
In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.
侵袭性念珠菌病的发病率不断上升以及对抗真菌治疗的耐药性促使我们寻找新的、更有效的抗真菌化合物。
研究2-环己叉基肼基-4-苯基噻唑（CPT）对白色念珠菌的抗真菌活性和毒性，并评估其潜在靶点。
在秀丽隐杆线虫中研究CPT对白色念珠菌生存的抗真菌活性。此外，我们测定了CPT对白色念珠菌黏附颊黏膜上皮细胞（BECs）能力的抑制作用、CPT在哺乳动物细胞中的毒性以及CPT在白色念珠菌中的潜在靶点。
CPT的最低抑菌浓度（MIC）值为0.4 - 1.9μg/mL。此外，高浓度（>60×MIC）的CPT在HepG2细胞中显示无毒性或低毒性，在人红细胞中的溶血率<1%。另外，CPT降低了酵母对BECs的黏附能力，并延长了感染白色念珠菌的秀丽隐杆线虫的存活时间。对CPT处理的细胞分析表明，其细胞壁比未处理的细胞薄，尤其是葡聚糖层。我们发现CPT处理的细胞中1,3-β-D-葡聚糖的含量明显低于未处理的细胞。对几种突变菌株进行的试验表明，CPT对1,3-β-葡聚糖合酶缺陷的酵母的抗真菌活性的MIC值较高。
总之，CPT似乎靶向白色念珠菌的细胞壁，在哺乳动物细胞中显示低毒性，并延长感染白色念珠菌的秀丽隐杆线虫的存活时间。
