Synthesis and biological evaluation of chalcone derivatives as neuroprotective agents against glutamate-induced HT22 mouse hippocampal neuronal cell death. Issue 22 (15th November 2020)

• Record Type: Journal Article
• Authors: Selvaraj, Baskar; Nguyen, Uyen Tran Tu; Huh, Gyewon; Nguyen, Duc Hung; Mok, Il-Kyoon; Lee, Heesu; Kang, Kyungsu; Bae, Ae Nim; Kim, Dae Won; Lee, Jae Wook
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 22(2020)
• Publication Date: 2020-11-15
• Subjects: HT22 cells -- MAPK -- AIF -- ROS -- Neuroprotection; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127597
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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.