Synthesis, biological evaluation and molecular modeling studies of substituted N-benzyl-2-phenylethanamines as cholinesterase inhibitors,New Journal of Chemistry

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Synthesis, biological evaluation and molecular modeling studies of substituted N-benzyl-2-phenylethanamines as cholinesterase inhibitors
New Journal of Chemistry ( IF 2.7 ) Pub Date : 2020-05-21 , DOI: 10.1039/d0nj00282h
Florencia Carmona-Viglianco _{1,

2,

3,

4,

5} , Daniel Zaragoza-Puchol _{6,

7,

8,

9,

10} , Oscar Parravicini _{2,

3,

4,

5,

11} , Adriana Garro _{2,

3,

4,

5,

11} , Ricardo D. Enriz _{2,

3,

4,

5,

11} , Gabriela E. Feresin _{6,

7,

8,

9,

10} , Marcela Kurina-Sanz _{1,

2,

3,

4,

5} , Alejandro A. Orden _{1,

2,

3,

4,

5}

Affiliation

In this work, we report the synthesis of a series of derivatives of N-benzyl-2-phenylethanamine which is the framework of norbelladine, the natural common precursor of the Amaryllidaceae alkaloids. These compounds were assessed in the inhibition of both AChE and BChE which are the enzymes responsible for the breakdown of acetylcholine and hence they constitute targets in the palliative treatment of Alzheimer's disease. In particular, brominated derivatives exhibited the lowest IC₅₀ values against AChE. Interestingly, the presence of iodine in one of the aromatic rings highly increased the inhibition of BChE compared to its analogues, with an IC₅₀ value similar to that of galantamine, which is the reference compound currently used in the treatment of AD. A possible mechanism of action for these compounds was determined by molecular modeling studies using combined techniques of docking and molecular dynamics simulations.

中文翻译：

取代的N-苄基-2-苯基乙胺作为胆碱酯酶抑制剂的合成，生物学评估和分子模型研究

在这项工作中，我们报告了N-苄基-2-苯基乙胺的一系列衍生物的合成，该衍生物是去甲贝拉定的骨架，而去甲贝拉定是石蒜科生物碱的天然常见前体。在抑制乙酰胆碱分解的酶AChE和BChE的抑制作用中评估了这些化合物，因此它们构成了姑息治疗阿尔茨海默氏病的靶标。特别是，溴化衍生物对AChE的IC ₅₀值最低。有趣的是，碘的在芳族环中的一个存在高度增加的BChE的抑制相比，它的类似物，与IC ₅₀值与加兰他敏相似，后者是目前用于治疗AD的参考化合物。这些化合物可能的作用机理是通过对接和分子动力学模拟相结合的分子模型研究确定的。

更新日期：2020-05-21

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