Design, Synthesis, and Antifungal Activity of Novel Conformationally Restricted Triazole Derivatives
Design, Synthesis, and Antifungal Activity of Novel Conformationally Restricted Triazole Derivatives
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新型构象限制性三唑衍生物的设计、合成和抗真菌活性
DOI：
10.1002/ardp.200900103
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发表时间：
2009-12-01
影响因子：
5.1
通讯作者：
Zhang, Wannian
中科院分区：
文献类型：
--
作者：
Wang, Wenya;Sheng, Chunquan;Zhang, Wannian
基于白念珠菌羊毛甾醇14 α-脱甲基酶（CACYP 51）的活性位点，设计并合成了一系列新的三唑衍生物。2-（2，4-二氟苯基）-3-（甲基（3-苯氧基烷基）氨基）-1-（1H-1，2，4-三唑-1-基）丙烷-2-醇类化合物对大多数测试的病原真菌显示出优异的体外活性。化合物8a对白色念珠菌的MIC 50值为0.01 μ M，这为进一步的结构优化提供了良好的起始模板。通过柔性分子对接研究了所设计化合物的结合模式。化合物通过疏水、范德华和氢键相互作用与CACYP 51相互作用。
A series of new triazole derivatives were designed and synthesized on the basis of the active site of lanosterol 14 alpha-demethylase from Candida albicans (CACYP51). 2-(2,4-Difluorophenyl)-3-(methyl(3-phenoxyalkyl)amino)-1-(1H-1,2,4-triazol-1-yl)propan-2-ols show excellent in-vitro activity against most of the tested pathogenic fungi. The MIC50 value of compound 8a against Candida albicans is 0.01 mu M, which provides a good starting template for further structural optimization. The binding modes of the designed compounds were investigated by flexible molecular docking. The compounds interacted with CACYP51 through hydrophobic, van-der-Waals, and hydrogen-bonding interactions.