單重態氧已被證實能夠抑制具有毒性的Tau蛋白聚合堆積,而不正常的tau聚集被認為是造成神經退化型疾病-阿茲海默症的主要原因之一。一般而言,釕金屬被認為有良好的生物相容性,而BODIPY則具有優越的可見光吸光能力。在本份研究中,我們設計並合成了三種帶有BODIPY基團的釕(II)金屬錯合物,並透過核磁共振儀以及X-ray解晶的方式確認這三種錯合物為結構異構物。其中,熱力學最穩定的異構物ε-Cl展現了光動力療法的特性,在可見光激發下,ε-Cl能夠有效地產生單重態氧。最重要的是,本研究發現這項化合物能夠透由照光激活單重態氧的方式,有效抑制神經細胞內Tau蛋白的聚合堆積,甚至在100 nM的濃度下抑制效果達到了42.53%。另一方面,我們也觀察到ε-Cl能夠大幅度的促進神經細胞的突觸增長,並且在突觸的長度與數量上都有顯著的正向影響。由於具有抑制Tau聚集以及促進神經細胞生長的能力,我們認為這類複合設計的有機金屬化合物是十分有潛力的抗阿茲海默藥物。
Singlet oxygen (1O2) has been identified as a key molecule against toxic tau aggregation, which is associated with the currently incurable Alzheimer’s disease (AD). Herein, we designed and synthesized three BODIPY-ruthenium conjugates, determined by X-ray crystallography and NMR spectroscopy as isomers. Under visible light irradiation, the thermodynamically favored form, ε-Cl can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy; an appreciable decrease to 42.53% at 100 nM. Moreover, the photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design as great potential therapeutics for Alzheimer’s disease.
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