Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives.

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Xu Y, Sheng C, Wang W, Che X, Cao Y, Dong G, Wang S, Ji H, Miao Z, Yao J, Zhang W

Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives.

Bioorg Med Chem Lett. 2010 May 1;20(9):2942-5. doi: 10.1016/j.bmcl.2010.03.014. Epub 2010 Mar 7.

PubMed ID

20362444 [ View in PubMed

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Abstract

In an attempt to find novel azole antifungal agents with improved activity and broader spectrum, computer modeling was used to design a series of new azoles with piperidin-4-one O-substituted oxime side chains. Molecular docking studies revealed that they formed hydrophobic and hydrogen-bonding interactions with lanosterol 14alpha-demethylase of Candida albicans (CACYP51). In vitro antifungal assay indicates that most of the synthesized compounds showed good activity against tested fungal pathogens. In comparison with fluconazole, itraconazole and voriconazole, several compounds (such as 10c, 10e, and 10i) show more potent antifungal activity and broader spectrum, suggesting that they are promising leads for the development of novel antifungal agents.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Voriconazole	Cytochrome P450 51	Protein	Yeast	Yes	Antagonist Inhibitor	Details