Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors
Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors
复制标题
苯并杂环N-肉豆蔻酰转移酶抑制剂等排类似物的设计、合成和抗真菌活性
DOI：
10.1016/j.ejmech.2010.03.007
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发表时间：
2010-09-01
影响因子：
6.7
通讯作者：
Zhang, Wannian
中科院分区：
文献类型：
--
作者：
Sheng, Chunquan;Xu, Hui;Zhang, Wannian
N-肉豆蔻酰转移酶（NMT）已成为设计具有新作用模式的新型抗真菌药物的有前途的新靶点。设计并合成了一系列苯并恶唑和吲哚衍生物作为苯并杂环NMT抑制剂的等排类似物。体外抗真菌试验表明苯并恶唑衍生物比吲哚更有效。分子对接研究表明，苯并杂环核心和 NMT 之间的氢键相互作用对于抑制剂定向到正确的位置可能至关重要。苯并恶唑衍生物8f的抗真菌活性与氟康唑相当或优于氟康唑，这可以作为进一步研究苯并杂环NMT抑制剂结构多样性的良好起点。 (C) 2010 Elsevier Masson SAS。版权所有。
N-myristoyltransferase (NMT) has been a promising new target for the design of novel antifungal agents with new mode of action. A series of benzoxazole and indole derivatives were designed and synthesized as isosteric analogues of benzoheterocyclic NMT Inhibitors. In vitro antifungal assay indicated that the benzoxazole derivatives were far more potent than the indoles. Molecular docking studies revealed that the hydrogen bonding interaction between the benzoheterocyclic core and NMT might be essential in the orientation of the inhibitor to a proper position. The antifungal activity of benzoxazole derivative 8f was comparable or superior to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the benzoheterocyclic NMT inhibitors. (C) 2010 Elsevier Masson SAS. All rights reserved.