A novel series of celecoxib derivatives were synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities for benefit in spinal cord injury (SCI). The title compounds were synthesized by conventional methods in good yields and subsequently tested for inhibitory activity against COX-1/COX-2. The most potent COX-2 inhibitor among the tested derivatives was further assayed for protective effect against experimental SCI of Sprague-Dawley rats. The designed compounds showed considerable inhibition of COX-2 as compared to COX-1 revealing compound 7m as most potent inhibitor of COX-2 isoenzyme (IC₅₀ = 0.04 µM). The expression of mitochondrial apoptotic genes (Bcl-2 and Bax) together with COX-2 and iNOS was restored near to normal as evidenced by western blot analysis in SCI rats. Taken altogether, compound 7m was identified as most potent inhibitor of COX-2. It also showed protective action against SCI via attenuation of COX-2, oxidative stress and apoptosis and inflammation in Male Sprague-Dawley rats.

合成了一系列新的塞来昔布衍生物，并评估了其对环氧合酶（COX-1 / COX-2）的抑制活性，从而有益于脊髓损伤（SCI）。通过常规方法以高收率合成标题化合物，随后测试其对COX-1 / COX-2的抑制活性。进一步测定了测试衍生物中最有效的COX-2抑制剂对Sprague-Dawley大鼠实验SCI的保护作用。与COX-1相比，所设计的化合物显示出对COX-2的显着抑制，表明化合物7m是最有效的COX-2同工酶抑制剂（IC ₅₀ = 0.04 µM）。蛋白质印迹分析表明，SCI大鼠体内线粒体凋亡基因（Bcl-2和Bax）以及COX-2和iNOS的表达恢复到接近正常水平。总而言之，化合物7m被确定为最有效的COX-2抑制剂。它还通过减弱COX-2，氧化应激，细胞凋亡和炎症对雄性Sprague-Dawley大鼠表现出针对SCI的保护作用。