Bettencourt Ana P, Castro Marián, Silva João P, Fernandes Francisco, Coutinho Olga P, Sousa Maria J, Proença Maria Fernanda, Areias Filipe M
Department of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Avenida de Barcelona 22, 15782 Santiago de Compostela, Spain.
Med Chem. 2019;15(4):341-351. doi: 10.2174/1573406414666181005143431.
Previous publications show that the addition of a phenolic antioxidant to an antifungal agent, considerably enhances the antifungal activity.
Synthesis of novel compounds combining phenolic units with linear or cyclic nitrogencontaining organic molecules with antioxidant/antifungal activity using methodologies previously developed in the group.
Several N- [1,2-dicyano-2- (arylidenamino) vinyl]-O-alkylformamidoximes 3 were synthesized and cyclized to 4,5-dicyano-N- (N´-alcoxyformimidoyl)-2-arylimidazoles 4 upon reflux in DMF, in the presence of manganese dioxide or to 6-cyano-8-arylpurines 5 when the reagent was refluxed in acetonitrile with an excess of triethylamine. These compounds were tested for their antioxidant activity by cyclic voltammetry, DPPH radical (DPPH•) assay and deoxyribose degradation assay. The minimum inhibitory concentration (MIC) of all compounds was evaluated against two yeast species, Saccharomyces cerevisiae and Candida albicans, and against bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram negative). Their cytotoxicity was evaluated in fibroblasts.
Among the synthetised compounds, five presented higher antioxidant activity than reference antioxidant Trolox and from these compounds, four presented antifungal activity without toxic effects in fibroblasts and bacteria.
Four novel compounds presented dual antioxidant/antifungal activity at concentrations that are not toxic to bacteria and fibroblasts. The active molecules can be used as an inspiration for further studies in this area.
先前的出版物表明，在抗真菌剂中添加酚类抗氧化剂可显著增强抗真菌活性。
利用该研究组先前开发的方法，合成将酚类单元与具有抗氧化/抗真菌活性的线性或环状含氮有机分子相结合的新型化合物。
合成了几种N-[1,2-二氰基-2-(亚芳基氨基)乙烯基]-O-烷基甲脒肟3，并在二氧化锰存在下于N,N-二甲基甲酰胺中回流环化生成4,5-二氰基-N-(N'-烷氧基甲亚胺基)-2-芳基咪唑4，或者当试剂在过量三乙胺存在下于乙腈中回流时生成6-氰基-8-芳基嘌呤5。通过循环伏安法、二苯基苦味酰基自由基（DPPH•）测定法和脱氧核糖降解测定法测试这些化合物的抗氧化活性。评估所有化合物对两种酵母菌种酿酒酵母和白色念珠菌以及对细菌枯草芽孢杆菌（革兰氏阳性）和大肠杆菌（革兰氏阴性）的最低抑菌浓度（MIC）。在成纤维细胞中评估它们的细胞毒性。
在合成的化合物中，有五种表现出比参考抗氧化剂Trolox更高的抗氧化活性，并且在这些化合物中，有四种表现出抗真菌活性，对成纤维细胞和细菌没有毒性作用。
四种新型化合物在对细菌和成纤维细胞无毒的浓度下呈现出双重抗氧化/抗真菌活性。这些活性分子可为该领域的进一步研究提供灵感。
