Synthesis and biological evaluation of chalcone derivatives as neuroprotective agents against glutamate-induced HT22 mouse hippocampal neuronal cell death.

Autor: Selvaraj B; Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; Convergent Research Center for Diagnosis, Treatment, and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology (UST), Daejun 34113, Republic of Korea., Nguyen UTT; Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea., Huh G; Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology (UST), Daejun 34113, Republic of Korea., Nguyen DH; Department of Biotechnology, Vietnam-Korea Institute of Science and Technology (VKIST), Hanoi, Viet Nam., Mok IK; Institute of Food Industrialization, Institutes of Green Bio Science & Technology and Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang-gun, Gangwon-do 25354, Republic of Korea., Lee H; Department of Anatomy, College of Dentistry, Gangnueng Wonju National University (GWNU), Gangneung 25457, Republic of Korea., Kang K; Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology (UST), Daejun 34113, Republic of Korea., Bae AN; Convergent Research Center for Diagnosis, Treatment, and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology (UST), Daejun 34113, Republic of Korea., Kim DW; Department of Biochemistry and Molecular Biology, College of Dentistry, Gangneung Wonju National University (GWNU), Gangneung 25457, Republic of Korea. Electronic address: kimdw@gwnu.ac.kr., Lee JW; Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; Convergent Research Center for Diagnosis, Treatment, and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology (UST), Daejun 34113, Republic of Korea. Electronic address: jwlee5@kist.re.kr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Nov 15; Vol. 30 (22), pp. 127597. Date of Electronic Publication: 2020 Oct 03.
DOI: 10.1016/j.bmcl.2020.127597
Abstrakt: Seventeen chalcone analogues were synthesized from 7-methoxy-3,4-dihydronaphthalen1(2H)-one and various aromatic aldehydes under basic conditions and their therapeutic properties were studied in mouse hippocampal cell line HT-22 against neuronal cell death induced by glutamate. From this study, we selected an analogue C01 as a active compound which showed significantly high neuroprotection. This compound inhibited Ca 2+ influx and reactive oxygen species (ROS) accumulation inside cells. The glutamate-induced cell death was analyzed by flow cytometry and it showed that C01 significantly reduced apoptotic or dead cell induced by 5 mM glutamate. Western blot analysis indicates that glutamate-mediated activation of MAPKs were inhibited by compound C01 treatment. In addition, the C01enhanced Bcl-2 and decreased Bax, the anti and pro apoptotic proteins respectively. Further analysis showed that, C01 prevented the nuclear translocation of AIF (apoptosis inducing factor) and inhibited neuronal cell death. Taken together, compound C01 treatment resulted in decreased neurotoxicity induced by 5 mM of glutamate. Our finding confirmed that compound C01 has neuro-therapeutic potential against glutamate-mediated neurotoxicity.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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