Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes Str. 2, D-06120 Halle (Saale), Germany.
Leibniz Institute of Plant Biochemistry, Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany.
Eur J Med Chem. 2017 Oct 20;139:222-231. doi: 10.1016/j.ejmech.2017.07.081. Epub 2017 Aug 2.
Piperlongumine B (19), an alkaloid previously isolated from long pepper (Piper longum) has been synthesized for the first time in a short sequence and in good yield together with 19 analogs. Screening of these compounds in Ellman's assays showed several of them to be good inhibitors of acetylcholinesterase while being less active for butyrylcholinesterase. Activity of the compounds increased with the ring size of the heterocycle, and a maximum of activity was observed for an analog holding 12 methylene groups in the aliphatic side chain. These compounds may be regarded as promising candidates for the development of efficient inhibitors of acetylcholinesterase being useful for the treatment of Alzheimer's disease.
倍半萜生物碱 Piperlongumine B（19），以前从长胡椒（Piper longum）中分离出来，首次以短序列和高产率合成，同时合成了 19 个类似物。这些化合物在 Ellman 测定法中的筛选结果表明，其中一些化合物是乙酰胆碱酯酶的良好抑制剂，而对丁酰胆碱酯酶的活性较低。化合物的活性随杂环的环尺寸而增加，在具有 12 个亚甲基的侧链中的类似物中观察到最大的活性。这些化合物可能被视为开发有效的乙酰胆碱酯酶抑制剂的有前途的候选物，对于治疗阿尔茨海默病非常有用。
