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微柱水仙,一种含胆碱酯酶抑制剂生物碱的石蒜科植物:海芒果胺骨架衍生物的构效分析

Clinanthus microstephium, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure-Activity Analysis of Haemanthamine Skeleton Derivatives.

作者信息

Adessi Tonino G, Borioni José L, Pigni Natalia B, Bastida Jaume, Cavallaro Valeria, Murray Ana P, Puiatti Marcelo, Oberti Juan C, Leiva Segundo, Nicotra Viviana E, Garcia Manuela E

机构信息

Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, XUA5000, Argentina.

Instituto Multidisciplinario de Biología Vegetal, IMBIV-CONICET, Córdoba, XUA5000, Argentina.

出版信息

Chem Biodivers. 2019 May;16(5):e1800662. doi: 10.1002/cbdv.201800662. Epub 2019 Apr 9.

DOI:10.1002/cbdv.201800662
PMID:30801949
Abstract

Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine-type compound (6-hydroxymaritidine) was tested as an inhibitor against acetyl- and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure-activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.

摘要

石蒜科植物不仅以其观赏价值闻名,还因其产生的生物碱而闻名。在本报告中,首次对酒杯花属植物进行了植物化学研究。采用气相色谱/质谱联用(GC/MS)和核磁共振(NMR)技术分析了小花酒杯花生物碱部分的化学成分。鉴定出了七种属于石蒜科生物碱三种结构类型的已知化合物。测试了一种海芒果胺型化合物(6-羟基马里替丁)的差向异构体混合物作为乙酰胆碱酯酶和丁酰胆碱酯酶(分别为AChE和BChE)的抑制剂,这两种酶在阿尔茨海默病治疗中具有相关性,结果良好。通过该生物碱与其他结构相关化合物的分子对接研究探讨了构效关系。

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