A magnetic beads-based ligand fishing method for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from Hunteria zeylanica

单胺氧化酶 化学 单胺氧化酶A 单萜 配体(生物化学) 吲哚试验 生物胺 立体化学 生物化学 血清素 受体
作者
Huaixin Liu,Jincai Wang,Sirui Yang,Wei Wang,Min Song,Xiao‐Qi Zhang,Jacques Crommen,Zhengjin Jiang,Tingting Zhang
出处
期刊:Journal of Chromatography A [Elsevier]
卷期号:1722: 464896-464896 被引量:2
标识
DOI:10.1016/j.chroma.2024.464896
摘要

In this study, a novel magnetic bead-based ligand fishing method was developed for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from natural products. In order to improve the screening efficiency, two different magnetic beads, i.e. amine and carboxyl terminated magnetic beads, were comprehensively compared in terms of their ability to immobilize monoamine oxidase A (MAOA), biocatalytic activity and specific adsorption rates for affinity ligands. Carboxyl terminated magnetic beads performed better for MAOA immobilization and demonstrated superior performance in ligand fishing. The MAOA immobilized magnetic beads were applied to screen novel monoamine oxidase inhibitors in an alkaloid-rich plant, Hunteria zeylanica. Twelve MAOA affinity ligands were screened out, and ten of them were identified as monoterpene indole alkaloids by HPLC-Obitrap-MS/MS. Among them, six ligands, namely geissoschizol, vobasinol, yohimbol, dihydrocorynanthenol, eburnamine and (+)-isoeburnamine which exhibited inhibitory activity against MAOA with low IC50 values. To further explore their inhibitory mechanism, enzyme kinetic analysis and molecular docking studies were conducted.
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