新型 12-羟基脱氢枞胺衍生物作为强效和选择性丁酰胆碱酯酶抑制剂。
Novel 12-hydroxydehydroabietylamine derivatives act as potent and selective butyrylcholinesterase inhibitors.
机构信息
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.
出版信息
Bioorg Chem. 2019 Sep;90:103092. doi: 10.1016/j.bioorg.2019.103092. Epub 2019 Jul 2.
The skeleton of the diterpene dehydroabietylamine was modified, and a set of 12-hydroxy-dehydroabietylamine derivatives was obtained. The compounds were screened in colorimetric Ellman's assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). Additional investigations concerning the enzyme kinetics were performed and showed 12-hydroxy-N-(4-nitro-benzoyl)dehydroabietylamine (13) and 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine (17) as selective BChE inhibitors holding good inhibition constants K = 0.72 ± 0.06 μM and K = 0.86 ± 0.19 μM, respectively.
对二萜去氢枞胺骨架进行修饰，得到了一组 12-羟基去氢枞胺衍生物。这些化合物在比色 Ellman 测定法中进行筛选，以确定它们作为乙酰胆碱酯酶（AChE，来自电鳗）和丁酰胆碱酯酶（BChE，来自马血清）抑制剂的能力。进行了关于酶动力学的进一步研究，结果表明 12-羟基-N-（4-硝基苯甲酰基）去氢枞胺（13）和 12-羟基-N-（异烟酰基）去氢枞胺（17）作为选择性 BChE 抑制剂，其抑制常数 K 分别为 0.72 ± 0.06 μM 和 0.86 ± 0.19 μM。
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