In this paper, we report the design, synthesis and biochemical evaluation of 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid 9, a myristicin derivative, from cheap and available vanillin as starting material. Compound 9 is identified as a potential precursor of natural brasiliamide derivatives. All the products are fully characterized. The crystal structure of the intermediate diethyl 2-acetamido-2-((7-methoxybenzo[d][1,3]dioxol-5-yl)methyl)malonate 16, a precursor of this amino acid, is obtained and presented. The interactions stabilizing the crystal packing of 16 were deeply analyzed by considering first the supramolecular stacking and finally, by analyzing the contacts descriptors on the Hirshfeld surface, the molecular fingerprint and the intermolecular energy. Different biochemical properties of the desired amino acid 9 and its selected precursors are investigated. In DPPH test, 9 showed the best anti-radical activity (IC₅₀ = 80.91 μM). The enzymatic, HRP-H₂O₂/L012, chemiluminescence assay reveals excellent inhibitory effect on the peroxidase activity and a good antioxidant activity of all the tested compounds with the best activity for 9 (IC₅₀ = 0.36 μM). The anti-peroxidase activity observed for compound 9 was confirmed by molecular docking exploration that allows to identify interactions in the HRP-9 complex. Docking results showed that 9 interacts with catalytic and active site residues, especially with Arg38, His42, Ser73, Phe68 and Pro139. Moreover, the inhibition of ROS production by activated HL-60 cells was moderately obtained with compounds 9 and 13. The MTS cell viability test reveals that all tested compounds, except myristicin aldehyde 13, were not cytotoxic indicating that the observed inhibition of ROS production of activated HL-60 cells was not due to cells death. Finally, physicochemical and ADME-Tox predictions suggested that compound 9 could be considered as promising drug candidate.

在本文中，我们报告了 2-amino-3-(7-methoxybenzo[ d ][1,3]dioxol-5-yl)propanoic acid 9的设计、合成和生化评价，这是一种肉豆蔻素衍生物，来自廉价且易得香兰素为起始原料。化合物9被确定为天然巴西酰胺衍生物的潜在前体。所有产品都具有充分的特征。获得并展示了中间体 2-乙酰氨基-2-((7-甲氧基苯并[ d ][1,3]二氧戊环-5-基)甲基)丙二酸二乙酯16的晶体结构，这是该氨基酸的前体。稳定16晶体堆积的相互作用通过首先考虑超分子堆积，最后通过分析 Hirshfeld 表面上的接触描述符、分子指纹和分子间能量进行了深入分析。研究了所需氨基酸9及其所选前体的不同生化特性。在DPPH测试中，9表现出最好的抗自由基活性（IC ₅₀  = 80.91 μM）。酶促、HRP-H ₂ O ₂ /L012、化学发光测定显示对所有测试化合物的过氧化物酶活性具有优异的抑制作用和良好的抗氧化活性，其中9的活性最佳(IC ₅₀  = 0.36 μM)。观察到的化合物的抗过氧化物酶活性9已通过分子对接探索得到证实，该探索允许识别 HRP- 9复合物中的相互作用。对接结果表明9与催化和活性位点残基相互作用，尤其是与Arg38、His42、Ser73、Phe68和Pro139相互作用。此外，用化合物9和13适度地抑制了活化的 HL-60 细胞对 ROS 产生的抑制。MTS 细胞活力测试表明，除了肉豆蔻醛13外，所有测试的化合物都没有细胞毒性，这表明观察到的对活化 HL-60 细胞的 ROS 产生的抑制不是由于细胞死亡。最后，物理化学和 ADME-Tox 预测表明化合物9 可以被认为是有前途的候选药物。