新型四氢萘类化合物合成及体外抗真菌活性研究

Synthesis and in vitro Antifungal Activity of Novel Tetralin Compounds

根据真菌羊毛甾醇14α-去甲基化酶的三维结构模型设计、合成了48个新型四氢萘类化合物,所有化合物的结构经过IR,1H NMR和MS确证.体外抗真菌活性研究表明所有化合物对7种临床致病真菌都有抗真菌活性,特别是化合物18,21,22,24的抗真菌活性最强.对接研究显示设计的先导化合物与靶酶活性腔中氨基酸功能残基结合,作用模式不同于氮唑类化合物.结果表明新型四氢萘类化合物是一类全新结构类型的抗真菌化合物.

Novel 2-aminotetralin compounds were designed and synthesized based on the three-dimensional model of lanosterol 14a-demethylase of Candida albicans. Their structures have been confirmed by IH NMR, IR and MS. All these compounds, especially compounds 18, 21, 22 and 24 exhibited potent antifungal activities against seven pathogenic fungi. The mode of the action of the lead compound was different from that of azoles, and the lead compound interacted with the amino acid residues in the active site. These aminotetralins provided lead compounds for the development of antifungal drugs.