title: New homoisoflavonoid analogues protect cells by regulating autophagy.
abstract: As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Li-She
authors.initials: LS
authors.lastname: Gan
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Lin-Wei
authors.initials: LW
authors.lastname: Zeng
authors.affiliation: School of Medicine, Zhejiang University City College, 48 Huzhou Road, Hangzhou 310015, China.
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Li
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: School of Medicine, Zhejiang University City College, 48 Huzhou Road, Hangzhou 310015, China. Electronic address: lijie@zucc.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans
chemical_list: D005419:Flavonoids
keywords: Autophagy; Cardioprotection; Homoisoflavonoid; Neuroprotection; Synthesis