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Synthesis and biological evaluation of quinoline/cinnamic acid hybrids as amyloid-beta aggregation inhibitors

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Abstract

The objective of the current study is to evaluate the potency of quinoline/cinnamic acid hybrids against amyloid-beta (Aβ) aggregation. In total, six new target quinoline/cinnamic acid hybrids were synthesized and screened for their in vitro anti-Aβ42 aggregation activity. Some hybrids, including (E)-N-(2-cinnamamidoethyl)-6,7-dimethoxyquinoline-2-carboxamide, (E)-6,7-dimethoxy-N-[2-[3-(4-methoxyphenyl)acrylamido]ethyl]quinoline-2-carboxamide, and (E)-6,7-dimethoxy-N-[2-[3-(2-methoxyphenyl)acrylamido]ethyl]quinoline-2-carboxamide, showed significant anti-Aβ42 aggregation activity. Molecular docking method was used to predict the binding modes of these compounds with Aβ42. In addition, their cytotoxicity towards neuroblastoma SH-SY5Y and human normal hepatocyte LO2 cells were tested. Neuroprotective evaluation demonstrated that these compounds could attenuate Aβ42-induced neurotoxicity towards SH-SY5Y cells in a dose-dependent manner. Overall, the present study provides quinoline/cinnamic acid hybrids as a new template for developing Aβ aggregation inhibitors against Alzheimer’s disease.

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Acknowledgements

This research work was financially supported by the Natural Science Foundation of China [no. 21672082], Natural Science Foundation of Shandong Province [nos. ZR2019YQ31, ZR2017BC101], and Shandong Talents Team Cultivation Plan of University Preponderant Discipline [no. 10027].

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Author notes

  1. Yong-Xi Ge and Zhi-Qiang Cheng contributed equally to this work.

Authors and Affiliations

  1. School of Biological Science and Technology, University of Jinan, Jinan, 250022, China

    Yong-Xi Ge, Zhi-Qiang Cheng, Lei Zhou, Hong-Xu Xie, Yin-Yin Wang & Cheng-Shi Jiang

  2. Shandong Key Laboratory of Biochemical Analysis, College of Chemistry and Molecular Engineering, Qingdao of University of Science and Technology, Qingdao, 266042, China

    Kongkai Zhu

  3. Shandong Institute for Food and Drug Control, Jinan, 250012, China

    Yang Jiao

  4. Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, 250012, China

    Guangpu Liu

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  1. Yong-Xi Ge
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Correspondence to Guangpu Liu or Cheng-Shi Jiang.

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Ge, YX., Cheng, ZQ., Zhou, L. et al. Synthesis and biological evaluation of quinoline/cinnamic acid hybrids as amyloid-beta aggregation inhibitors. Monatsh Chem 151, 845–852 (2020). https://doi.org/10.1007/s00706-020-02609-2

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  • DOI: https://doi.org/10.1007/s00706-020-02609-2

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