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  • Title: Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors.
    Author: Sheng C, Xu H, Wang W, Cao Y, Dong G, Wang S, Che X, Ji H, Miao Z, Yao J, Zhang W.
    Journal: Eur J Med Chem; 2010 Sep; 45(9):3531-40. PubMed ID: 20615585.
    Abstract:
    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.
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