Synthesis of 2,5-Diaryl- Substituted Thiophenes as Helical Mimetics: Towards the Modulation of Islet Amyloid Polypeptide ( IAPP) Amyloid Fibril Formation and Cytotoxicity
Synthesis of 2,5-Diaryl- Substituted Thiophenes as Helical Mimetics: Towards the Modulation of Islet Amyloid Polypeptide ( IAPP) Amyloid Fibril Formation and Cytotoxicity
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DOI：
10.1002/chem.201303928
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发表时间：
2014-02-24
影响因子：
4.3
通讯作者：
Forgione, Pat
中科院分区：
文献类型：
--
作者：
Hassanpour, Avid;De Carufel, Carole Anne;Forgione, Pat
合成了一系列2，5-二芳基噻吩类化合物作为β-螺旋的小分子模拟物，以调节胰岛淀粉样多肽（IAPP）的淀粉样蛋白生成和细胞毒性作用。3-取代的噻吩-2-羧酸被用作关键中间体，并通过钯脱羧交叉偶联和直接CH活化连续官能化，总收率为23 - 95%。配体对IAPP淀粉样蛋白原纤维形成的影响用基于硫黄素T（ThT）荧光的测定法进行评价。此外，这些化合物抑制IAPP的细胞毒性作用的能力进行了评估，使用胰腺细胞。
A range of 2,5-diarylated thiophenes were synthesised as small molecule mimetics of the -helix to modulate the amyloidogenesis and cytotoxic effect of islet amyloid polypeptide (IAPP). 3-Substituted thiophene-2-carboxylic acids were used as key intermediates and functionalised by palladium decarboxylative cross-coupling and direct CH activation successively with overall yields ranging from 23 to 95%. The effect of the ligands on IAPP amyloid fibril formation was evaluated with the thioflavinT (ThT) fluorescence-based assay. Furthermore, the capacity of these compounds to inhibit the cytotoxic effect of IAPP was assessed using -pancreatic cells.