New homoisoflavonoid analogues protect cells by regulating autophagy

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 6; pp. 1441 - 1445
• Main Authors: Gan, Li-She, Zeng, Lin-Wei, Li, Xiang-Rong, Zhou, Chang-Xin, Li, Jie
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.03.2017; Elsevier
• Subjects: Autophagy; Autophagy - drug effects; Cardioprotection; Cell Line, Tumor; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytoprotection - drug effects; Flavonoids - pharmacology; Homoisoflavonoid; Humans; Life Sciences & Biomedicine; Neuroprotection; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Synthesis; Homoisoflavonoid; Neuroprotection; Synthesis; Cardioprotection; Autophagy; OPHIOPOGON-JAPONICUS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.01.086

A series of homoisoflavonoid derivatives were designed and synthesized for the development of drug candidates for cell protective activities. [Display omitted] 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.