Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole

作者：Dai, Li; Zang, Chengxu; Tian, Shujuan; Liu, Wei; Tan, Shanlun; Cai, Zhan; Ni, Tingjunhong; An, Maomao; Li, Ran; Gao, Yue; Zhang, Dazhi^*; Jiang, Yuanying

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(1): 34-37.

DOI：10.1016/j.bmcl.2014.11.022

• Caffeic acid
• Synergistic activity
• Fluconazole-resistant Candida albicans
• Structure-activity relationship

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 mu g/ml, decreased the MIC80 of fluconazole from 128.0 mu g/ml to 1.0-0.5 mu g/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

• 出版日期2015-1-1
• 单位同济大学; 中国人民解放军第二军医大学