Identification of 2-subsituted benzothiazole derivatives as triple-functional agents with potential for AD therapy
Identification of 2-subsituted benzothiazole derivatives as triple-functional agents with potential for AD therapy
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DOI：
10.1039/c5ra25788c
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发表时间：
2016-02
期刊：
影响因子：
3.9
通讯作者：
Liu-Ying Jiang;Min-Kui Zhang;L. Tang;Qinjie Weng;Yanhong Shen;Yongzhou Hu;R. Sheng
中科院分区：
文献类型：
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作者：
Liu-Ying Jiang;Min-Kui Zhang;L. Tang;Qinjie Weng;Yanhong Shen;Yongzhou Hu;R. Sheng
采用药效团结合的策略，设计合成了一系列新型2-取代苯并噻唑类MTDL药物。将来自ThT的苯并噻唑部分和来自去铁酮的HPO部分与乙烯基连接体连接以获得目标化合物。生物学评价结果显示，大多数化合物具有同时干扰Aβ聚集、氧化应激和金属代谢紊乱的三重功能。化合物9 c和9 i具有良好的自身A β1-42聚集抑制活性、ABTS stec+清除活性、生物金属螯合活性以及对Aβ1-42纤维的解聚活性。除了这些优点外，它们在高达50 μM的浓度下对人胶质瘤U251细胞均无细胞毒性，因此值得进一步研究。
A novel series of 2-subsituted benzothiazole derivatives as MTDLs were designed and synthesized for AD therapy using pharmacophore-combine strategy. The benzothiazole moiety from ThT and the HPO moiety from deferiprone were connected with vinyl linker to achieve target compounds. The biological evaluation results revealed that the majority of them demonstrated desirable triple functions by interfering with Aβ aggregation, oxidative stress and metal dyshomeostasis simultaneously. The two most attractive compounds 9c and 9i exhibited excellent self-Aβ1–42 aggregation inhibitory activity, efficient ABTS˙+ scavenging activity, potent biometals chelating properties, as well as disaggregation activity against previous formed Aβ1–42 fibrils. In addition to these advantages, both of them displayed no cytotoxicity to human glioma U251 cells up to 50 μM, thereby meriting further investigation.