Umbelliferone has been demonstrated to have a wide range of biological activities. However, the effect of incorporating a formyl moiety in the umbelliferone scaffold has not been investigated. In this paper, we investigated the inhibitory activity of six coumarins, namely umbelliferone (1), 6-formyl umbelliferone (2), 8-formyl umbelliferone (3), umbelliferone-6-carboxylic acid (4), esculetin (5), and scopoletin (6) against human monoamine oxidases (hMAOs), self-amyloid β (Aβ) aggregation, and lipid peroxidation. We found that all compounds had high selectivity for hMAO-A in comparison with hMAO-B. Among the compounds, 2 exhibited the highest hMAO inhibitory activity with an IC₅₀ value of 3.23 µM for hMAO-A and 15.31 µM for hMAO-B. Enzyme kinetic analysis showed that 2 and 3 were competitive hMAO inhibitors. In silico hydrated molecular docking simulations revealed that the coumarins interacted with substrate-binding site residues of the enzymes and the isoalloxazine ring of FAD. In addition, formyl coumarins 2 and 3 significantly inhibited lipid peroxidation in rat brain homogenates and self-Aβ_25-35 aggregation compared to other derivatives. These represent the first experimental and modelling data for hMAO-A/B inhibition by umbelliferone derivatives. Together, the data suggest that introduction of a formyl moiety in the 7-hydroxycoumarin scaffold, especially at the 6 position, plays an important role in the inhibition of hMAOs, Aβ self-aggregation, and lipid peroxidation. Umbelliferone derivative 2 is a promising therapeutic lead scaffold for developing anti-neuropsychiatric disorder drugs that function via selective hMAO-A inhibition.

伞形酮已被证明具有广泛的生物活性。然而，尚未研究将甲酰基部分掺入伞形酮支架中的作用。在本文中，我们研究了六种香豆素的抑制活性，即伞形酮（1），6-甲酰基伞形酮（2），8-甲酰基伞形酮（3），伞形酮-6-羧酸（4），七叶皂甙（5），和scopoletin（6）抗人单胺氧化酶（h MAOs），自身淀粉样β（Aβ）聚集和脂质过氧化作用。我们发现与h相比，所有化合物对h MAO-A的选择性都高MAO-B。在化合物，2表现出最高的ħ MAO抑制活性用IC ₅₀ 3.23μM的对值ħ MAO-A和15.31μM为ħ MAO-B。酶动力学分析表明，2和3是竞争性h MAO抑制剂。在计算机水合分子对接模拟中发现，香豆素与酶的底物结合位点残基和FAD的异恶嗪环相互作用。此外，甲酰香豆素2和3大鼠脑组织匀浆和自我Aβ显著抑制脂质过氧化_25-35与其他衍生产品相比 这些代表了伞形酮衍生物抑制h MAO-A / B的第一个实验和模型数据。总之，数据表明在7-羟基香豆素支架中，特别是在6位引入甲酰基部分，在抑制h MAO，Aβ自聚集和脂质过氧化中起重要作用。伞形酮衍生物2是用于开发抗神经精神疾病药物的有前途的治疗先导支架，该药物通过选择性的h MAO-A抑制而起作用。