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当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

用于预防和治疗阿尔茨海默病的新型加兰他敏 - 肽衍生物的合成

卷 16, 期 3, 2019

页: [183 - 192] 页: 10

弟呕挨: 10.2174/1567205016666190228123923

价格: $65

摘要

背景:虽然目前尚无对阿尔茨海默病的有效治疗方法,但一些作为乙酰胆碱酯酶抑制剂的药物,如加兰他敏,对这类患者有积极的影响。 β-和/或γ-分泌酶抑制剂是另一种潜在的药物。在这里,我们报告了新的肽 - 加兰他敏衍生物的合成,具有预期的对乙酰胆碱酯酶和β-分泌酶的抑制活性。 目的:这项工作的目的是获得加兰他敏的新肽衍生物,与加兰他敏相比毒性降低。 方法:使用片段缩合方法在溶液中进行合成。新衍生物的特征在于熔点,旋光角,NMR和质谱。根据标准方案,对小鼠测定急性毒性。通过标准的基于MTT的比色法,在一组人(HEP-G2,BV-173)和鼠(Neuro-2a)肿瘤细胞系中体外测试所有新化合物的细胞毒活性。 结果:含有缩短的β-分泌酶抑制剂类似物(Boc-Asn-Leu-Ala-Val-OH)和烟碱或异烟碱残基的新的加兰他敏衍生物,均与接头(L-Asp)连接到加兰他敏的11位。获得。发现一些新化合物的体内毒性高达1000mg / kg。针对肿瘤细胞系的细胞毒性筛选显示加兰他敏衍生物的生长抑制性质可忽略不计。 结论:报道了包含肽部分和烟酸或异烟酸的新加兰他敏衍生物的合成。急性毒性研究表明它们的毒性比加兰他敏低约100倍。该效果归因于肽片段。细胞毒性研究表明与低毒性结果具有良好的相关性。这些结果对于将这类化合物用作药物是令人鼓舞的。

关键词: 加兰他敏,阿尔茨海默病,烟酸,异烟酸,毒性,细胞毒性。

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