New homoisoflavonoid analogues protect cells by regulating autophagy
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 Chi...
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Published in | Bioorganic & medicinal chemistry letters Vol. 27; no. 6; pp. 1441 - 1445 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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15.03.2017
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Abstract | 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. |
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AbstractList | 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. 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. 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 H O -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. 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 P13K signaling pathway. (C) 2017 Elsevier Ltd. All rights reserved. |
Author | Gan, Li-She Li, Xiang-Rong Zeng, Lin-Wei Zhou, Chang-Xin Li, Jie |
Author_xml | – sequence: 1 givenname: Li-She surname: Gan fullname: Gan, Li-She organization: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China – sequence: 2 givenname: Lin-Wei surname: Zeng fullname: Zeng, Lin-Wei organization: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China – sequence: 3 givenname: Xiang-Rong surname: Li fullname: Li, Xiang-Rong organization: School of Medicine, Zhejiang University City College, 48 Huzhou Road, Hangzhou 310015, China – sequence: 4 givenname: Chang-Xin surname: Zhou fullname: Zhou, Chang-Xin organization: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China – sequence: 5 givenname: Jie surname: Li fullname: Li, Jie email: lijie@zucc.edu.cn organization: School of Medicine, Zhejiang University City College, 48 Huzhou Road, Hangzhou 310015, China |
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Keywords | Homoisoflavonoid Neuroprotection Synthesis Cardioprotection Autophagy OPHIOPOGON-JAPONICUS |
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Snippet | 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... |
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SubjectTerms | 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 |
Title | New homoisoflavonoid analogues protect cells by regulating autophagy |
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