Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
Department of Electrical and Electronic Engineering, University of Cagliari 09123 Cagliari, Italy.
Bioorg Chem. 2021 Feb;107:104616. doi: 10.1016/j.bioorg.2020.104616. Epub 2021 Jan 5.
A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC = 0.024 µM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC = 0.168 µM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition.
设计并合成了一系列新的 2-苯基苯并呋喃衍生物，以确定与 MAO 抑制活性和选择性相关的结构特征。在 2-苯基环中引入甲氧基取代基，而苯并呋喃部分则未取代或在 5 或 7 位用硝基取代。苯环和苯并呋喃部分的取代模式决定了对 MAO-A 或 MAO-B 的亲和力。在这一系列中，2-(3-甲氧基苯基)-5-硝基苯并呋喃 9 是最有效的 MAO-B 抑制剂（IC = 0.024 µM），而 7-硝基-2-苯基苯并呋喃 7 是最有效的 MAO-A 抑制剂（IC = 0.168 µM），两者均为可逆抑制剂。2-苯基环上甲氧基的数量和位置对抑制活性有重要影响。分子对接研究证实了实验结果，并强调了关键残基在酶抑制中的重要性。
