Design And Development Of Novel Thiazolidin-4-One-1,3,5-Triazine Derivatives As Neuro-Protective Agent Against Cerebral Ischemiareperfusion Injury In Mice Via Attenuation Of Nf-Kappa B

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-kappa B transcriptional activity in LPS-stimulated RAW264.7 cells, displaying compound8kas 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 compound8kcauses attenuation of inflammation (TNF-alpha, IL-beta, 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 compound8kpre-treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro-protective agent by inactivation of NF-kappa B.