苯并噻唑-内过氧化物共轭物通过单线态氧介导的纤维氧化解毒作用保护 PC12 细胞免受 β 淀粉样蛋白诱导的细胞死亡影响

Hao Wu, Lei Wang, Xiao Qian, Wanwan Wang, Yu Si, Rensong Sun, Engin U. Akkaya
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摘要

我们设计并合成了以β-淀粉样蛋白纤维为目标的苯并噻唑分子的可转移内过氧化物。研究表明,这些内过氧化物通过热环化反应释放出的单线态氧能使淀粉样蛋白组合物的结构发生显著变化。最重要的是,在有内过氧化物存在的情况下,β-淀粉样蛋白纤维对 PC12 细胞的细胞毒性显著降低。这一观察结果,再加上这种转变既不需要外部氧气,也不需要光照这一事实,都非常令人期待。
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Benzothiazole-endoperoxide conjugates protect PC12 cells against β-amyloid-induced cell death via singlet oxygen mediated oxidative detoxification of fibrils
Metastable endoperoxides with beta-amyloid fibrils targeting benzothiazole moieties were designed and synthesized. Singlet oxygen released from these endoperoxides by thermal cycloreversion reaction was shown to cause significant structural changes on the amyloid assemblies. Most importantly, the cytotoxicity of the beta-amyloid fibrils on the PC12 cells were significantly reduced in the presence of endoperoxides. This observation, coupled with the fact that neither external oxygen, nor light is needed for this transformation, is very promising.
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