Department of "Biotecnologie, Chimica e Farmacia", "Università degli Studi di Siena", Via A. Moro 2, 53100 Siena, Italy.
Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
Eur J Med Chem. 2014 Aug 18;83:665-73. doi: 10.1016/j.ejmech.2014.07.001. Epub 2014 Jul 1.
A new series of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives was synthesized. The antifungal activity was evaluated in vitro against different fungal species. The biological results show that the most active compounds possess an antifungal activity comparable or higher than Fluconazole against Candida albicans, non-albicans Candida species, Cryptococcus neoformans and dermathophytes. Because of their racemic nature, the most active compounds 5f and 6c were tested as pure enantiomers. For 6c the (R)-enantiomer resulted more active than the (S)-one, otherwise for 5f the (S)-enantiomer resulted the most active. To rationalize the experimental data, a ligand-based computational study was carried out; the results of the modelling study show that (S)-5f and (R)-6c perfectly align to the ligand-based model, showing the same relative configuration. Preliminary studies on the human lung adenocarcinoma epithelial cells (A549) have shown that 6c, 5e and 5f possess a low cytotoxicity.
我们合成了一系列新的 2-(1H-咪唑-1-基)-1-苯乙醇衍生物。在体外对不同的真菌物种进行了抗真菌活性评估。生物实验结果表明，最具活性的化合物对白色念珠菌、非白色念珠菌念珠菌属、新型隐球菌和皮肤真菌具有与氟康唑相当或更高的抗真菌活性。由于它们的外消旋性质，最具活性的化合物 5f 和 6c 被测试为纯对映异构体。对于 6c，(R)-对映异构体比(S)-对映异构体更具活性，而对于 5f，(S)-对映异构体则最具活性。为了合理化实验数据，我们进行了基于配体的计算研究；模型研究的结果表明，(S)-5f 和 (R)-6c 与基于配体的模型完全一致，具有相同的相对构型。对人肺腺癌细胞(A549)的初步研究表明，化合物 6c、5e 和 5f 具有较低的细胞毒性。
