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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
奥尔莫西安A-P,结构多样化的诺利齐丁类化物,具有来自Ormosia yunnanensis的ACHE抑制作用
Qiong Jin1,2, Xu-Jie Qin1,2, Wen-Jie Sun1,2
1State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.
在Ormosia yunnanensis中发现了16种新的化,其中一些具有强大的乙胆酶 (AChE) 抑制作用. 一种新型化合物奥尔莫西亚宁A显示出显著的AChE抑制活性,这表明了潜在的治疗应用.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 奎诺利胺类化合物 (QA) 是一类具有各种生物活性的多样化天然产品.
- *Ormosia*属是已知的生物活性QA的来源.
- 了解来自Ormosia yunnanensis的QA的结构多样性和生物活性具有科学意义.
研究的目的:
- 从Ormosia yunnanensis*中分离和表征新的化类化物.
- 为了研究分离化合物的乙胆酶 (AChE) 抑制活性.
- 阐明QA与ACHE抑制的结构-活性关系.
主要方法:
- 使用染色体技术分离和净化QA.
- 使用光谱方法 (NMR,MS) 和计算分析 (ECD计算) 阐明结构.
- 在体外乙胆化酶 (AChE) 抑制试验和分子对接研究.
主要成果:
- 隔离了16种新的QA,命名为ormosianines A-P (1-16),以及18种已知的同源 (17-34).
- 奥尔莫氨酸A (1) 和B (2) 代表具有裂开的皮佩里丁环的新型结构类型.
- 五环*奥莫西亚*类型的QA,包括奥莫西亚A (1),表现出显著的ACHE抑制活性,IC50值低至1.55μM的化合物1.
- 分子对接表明奥尔莫西安因A与ACHE (蛋白1DX4) 的潜在结合.
结论:
- 这项研究扩大了已知诺利胺类化合物的结构多样性.
- 几种Ormosia类型的QA,特别是Ormosianine A,是乙胆酶的强有力的抑制剂.
- 这些发现凸显了Ormosia yunnanensis作为新型ACHE抑制剂的来源,用于治疗开发的潜力.
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