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

A series of caffeic acid amides 3-13 were designed and synthesized through scaffold hopping from berbeine and 2, 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. The SAR study indicates that the dihydroxyl groups and the amido group in the caffeic acid amides are the important pharmacophores.