Synthesis and biological evaluation of isoliquiritigenin derivatives as a neuroprotective agent against glutamate mediated neurotoxicity in HT22 cells. Issue 8 (15th April 2020)

• Record Type: Journal Article
• Authors: Selvaraj, Baskar; Kim, Dae Won; Huh, Gyuwon; Lee, Heesu; Kang, Kyungsu; Lee, Jae Wook
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 8(2020)
• Publication Date: 2020-04-15
• Subjects: Isoliquirtigenin -- Glutamate induced neurotoxicity -- HT22 mouse hippocampal neuronal cells -- MAPKs -- AIF; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127058
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Glutamate-induced neurotoxicity is characterized by cellular Ca 2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca 2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca 2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11 . We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.