title: Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.
abstract: 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 μg/ml, decreased the MIC₈₀ of fluconazole from 128.0 μg/ml to 1.0-0.5 μg/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.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Dai
authors.forename: Chengxu
authors.initials: C
authors.lastname: Zang
authors.forename: Shujuan
authors.initials: S
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Shanlun
authors.initials: S
authors.lastname: Tan
authors.forename: Zhan
authors.initials: Z
authors.lastname: Cai
authors.forename: Tingjunhong
authors.initials: T
authors.lastname: Ni
authors.forename: Maomao
authors.initials: M
authors.lastname: An
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000737:chemistry*; D002109:Caffeic Acids / Q000008:administration & dosage / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D015725:Fluconazole / Q000008:administration & dosage / Q000737:chemistry*; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: D000577:Amides; D002109:Caffeic Acids; D015725:Fluconazole; C040048:caffeic acid