title: [Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans].
abstract: Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Tian
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Cheng-Xu
authors.initials: CX
authors.lastname: Zang
authors.forename: Zhan
authors.initials: Z
authors.lastname: Cai
authors.forename: Ting-jun-hong
authors.initials: TJ
authors.lastname: Ni
authors.forename: Shan-Lun
authors.initials: SL
authors.lastname: Tan
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Cao
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D007546:Isoquinolines; D001599:Berberine; D015725:Fluconazole; C039109:isoquinoline