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.

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.