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

Yulan Xu, Chunquan Sheng, Wenya Wang, Xiaoying Che, Yongbing Cao, Guoqiang Dong, Shengzheng Wang, Haitao Ji, Zhenyuan Miao, Jianzhong Yao, Wannian Zhang

School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.

Bioorganic & medicinal chemistry letters 2010 May 1

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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. 2010. Published by Elsevier Ltd.

Citation

Yulan Xu, Chunquan Sheng, Wenya Wang, Xiaoying Che, Yongbing Cao, Guoqiang Dong, Shengzheng Wang, Haitao Ji, Zhenyuan Miao, Jianzhong Yao, Wannian Zhang. Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives. Bioorganic & medicinal chemistry letters. 2010 May 1;20(9):2942-5