Novel conformationally restricted triazole derivatives with potent antifungal activity

作者：Wang Wenya; Wang Shengzheng; Liu Yang; Dong Guoqiang; Cao Yongbing; Miao Zhenyuan; Yao Jianzhong; Zhang Wannian^*; Sheng Chunquan

来源：European Journal of Medicinal Chemistry, 2010, 45(12): 6020-6026.

DOI：10.1016/j.ejmech.2010.09.070

• Azole
• Rational design
• Conformationally restricted analogues
• Molecular docking
• Antifungal activity

In continuation of our work on azole antifungal agents, a series of new conformationally restricted triazole derivatives possessing benzylpiperidin-4-yl methyl amino side chains were designed and synthesized. All the new azoles showed moderate to excellent in vitro antifungal activity against most of the tested pathogenic fungi. Several compounds (such as 12e, 12f, 12h and 12n) showed higher antifungal activity against Candida albicans than fluconazole. Moreover, compounds 12g-i also showed good activity against Aspergillus fumigatus with their MIC(80) on the level of 1 mu g/mL Flexible molecular docking was used to analyze the binding mode of the designed compounds. They interact with CACYP51 through hydrophobic and van der Wools interactions.

• 出版日期2010-12
• 单位中国人民解放军第二军医大学