Medina-Alarcón Kaila P, Singulani Junya L, Voltan Aline R, Sardi Janaina C O, Petrônio Maicon S, Santos Mariana B, Polaquini Carlos R, Regasini Luis O, Bolzani Vanderlan S, da Silva Dulce H S, Chorilli Marlus, Mendes-Giannini Maria J S, Fusco-Almeida Ana M
Mycology Laboratory and Nucleus of Proteomics, Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State UniversityAraraquara, Brazil.
Department of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University, São José do Rio PretoAraraquara, Brazil.
Front Microbiol. 2017 Jun 12;8:1048. doi: 10.3389/fmicb.2017.01048. eCollection 2017.
Dodecyl protocatechuate (dodecyl) is a derivative of protocatechuic acid (3,4-dihydroxybenzoic acid) that possesses anti-oxidant and antifungal properties. Nanostructured lipid systems (NLS) can potentiate the action of many antifungal agents, reducing the required dose and side effects by improving their activity. This work aimed to evaluate dodecyl protocatechuate loaded into a NLS (NLS+dodecyl) as a strategy for the treatment of and Antifungal activity against and was evaluated using the microdilution technique. NLS+dodecyl showed high antifungal activity with a minimum inhibitory concentration ranging from 0.06 to 0.03 μg/mL; 4- to 16-fold higher than that of free dodecyl. NLS+dodecyl was able to inhibit fungal adhesion of the extracellular artificial matrix proteins (laminin and fibronectin), resulting in 82.4 and 81% inhibition, respectively, an increase of 8-17% compared with free dodecyl. These findings corroborate previous results demonstrating 65 and 74% inhibition of fungal adhesion in pulmonary fibroblast cells by dodecyl and NLS+dodecyl, respectively, representing a 9% increase in inhibition for NLS+dodecyl. Subsequently, cytotoxicity was evaluated using the 0.4% sulforhodamine B assay. NLS+dodecyl did not exhibit cytotoxicity in MRC5 (human pneumocyte) and HepG2 (human hepatic carcinoma) cells, thus increasing the selectivity index for NLS+dodecyl. In addition, cytotoxicity was evaluated using the model; neither dodecyl nor NLS+dodecyl exhibited any toxic effects. Taken together, these results suggest that NLS can be used as a strategy to improve the activity of dodecyl against and because it improves antifungal activity, increases the inhibition of fungal adhesion in lung cells and the extracellular matrix , and does not exhibit any toxicity both and .
十二烷基原儿茶酸（十二烷基）是原儿茶酸（3,4 - 二羟基苯甲酸）的衍生物，具有抗氧化和抗真菌特性。纳米结构脂质体系（NLS）可以增强许多抗真菌剂的作用，通过提高其活性来降低所需剂量和副作用。这项工作旨在评估负载于NLS中的十二烷基原儿茶酸（NLS + 十二烷基）作为治疗[具体疾病名称缺失]的一种策略。使用微量稀释技术评估了其对[具体真菌名称缺失]和[具体真菌名称缺失]的抗真菌活性。NLS + 十二烷基表现出高抗真菌活性，最低抑菌浓度范围为0.06至0.03μg/mL；比游离十二烷基高4至16倍。NLS + 十二烷基能够抑制真菌对细胞外人工基质蛋白（层粘连蛋白和纤连蛋白）的黏附，分别导致82.4%和81%的抑制率，与游离十二烷基相比增加了8 - 17%。这些发现证实了先前的结果，即十二烷基和NLS + 十二烷基分别对肺成纤维细胞中的真菌黏附具有65%和74%的抑制率，NLS + 十二烷基的抑制率提高了9%。随后，使用0.4%的磺酰罗丹明B测定法评估细胞毒性。NLS + 十二烷基在MRC5（人肺细胞）和HepG2（人肝癌细胞）中未表现出细胞毒性，从而提高了NLS + 十二烷基的选择性指数。此外，使用[具体模型名称缺失]模型评估细胞毒性；十二烷基和NLS + 十二烷基均未表现出任何毒性作用。综上所述，这些结果表明NLS可作为一种策略来提高十二烷基对[具体真菌名称缺失]和[具体真菌名称缺失]的活性，因为它提高了抗真菌活性，增加了对肺细胞和细胞外基质中真菌黏附的抑制作用，并且在[具体方面缺失]和[具体方面缺失]均未表现出任何毒性。
