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Design and development of novel thiazolidin‐4‐one‐1,3,5‐triazine derivatives as neuro‐protective agent against cerebral ischemia–reperfusion injury in mice via attenuation of NF‐ĸB
Author(s) -
Lu Min,
Qi Yujun,
Han Yu,
Yi Qiong,
Xu Lei,
Sun Wenlin,
Ni Guihua,
Ni Xiaoyu,
Xu Changsong
Publication year - 2020
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13744
Subject(s) - pharmacology , in vivo , ischemia , oxidative stress , chemistry , apoptosis , inflammation , nf κb , medicine , biochemistry , immunology , biology , microbiology and biotechnology
The present study enumerates the discovery and development of novel thiazolidin‐4‐one‐1,3,5‐triazine as neuro‐protective agent against cerebral ischemia–reperfusion injury in mice. These compounds showed significant inhibition of NF‐ĸB transcriptional activity in LPS‐stimulated RAW264.7 cells, displaying compound 8k as most potent inhibitor among the tested derivative. The compound 8k was further studied in in vivo middle cerebral artery occlusion (MCAO) mice model for neuro‐protective action. Results suggest that compound 8k causes attenuation of inflammation (TNF‐α, IL‐β, and IL‐6), oxidative stress (SOD, GSH, and MDA), and apoptosis (Bcl‐2, Bax, and cleaved caspase‐3) in MCAO mice in concentration‐dependent manner. Collectively, our results documented that compound 8k pre‐treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro‐protective agent by inactivation of NF‐ĸB.