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.

中文翻译：

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设计和开发新型 thiazolidin-4-one-1,3,5-triazine 衍生物作为神经保护剂，通过减弱 NF-ĸB 来对抗小鼠脑缺血再灌注损伤。

本研究列举了新型噻唑烷-4-one-1,3,5-三嗪作为小鼠脑缺血再灌注损伤的神经保护剂的发现和开发。这些化合物在 LPS 刺激的 RAW264.7 细胞中显示出对 NF-ĸB 转录活性的显着抑制，显示化合物8k是测试衍生物中最有效的抑制剂。在体内大脑中动脉闭塞 (MCAO) 小鼠模型中进一步研究了化合物8k 的神经保护作用。结果表明，化合物8k在 MCAO 小鼠中引起炎症（TNF-α、IL-β 和 IL-6）、氧化应激（SOD、GSH 和 MDA）和细胞凋亡（Bcl-2、Bax 和裂解的 caspase-3）的减弱依赖方式。总的来说，我们的结果证明化合物8k预处理可以保护脑 I/R。这种新型铅支架可能有助于通过灭活 NF-ĸB 来研究新的神经保护剂。