Vessel-Organ Interaction Research Center, VOICE (MRC), College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.
Biotechnology Department, Vietnam - Korea Institute of Science and Technology, Thach Hoa, Thach That, Hanoi, Vietnam.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2251099. doi: 10.1080/14756366.2023.2251099.
Two new neolignans, myrifralignans F-G ( and ), four new diarylnonanoid derivatives, myrifragranones A-D (-), and 18 known compounds were isolated and structurally elucidated from nutmeg ( Houtt.) seeds. The absolute configurations of these secondary metabolites were determined using the electronic circular dichroism technique. The inhibitory potential of these isolated compounds on soluble epoxide hydrolase (sEH) was investigated for the first time. Among them, malabaricones B and C ( and ) and four new compounds - displayed inhibitory activities against sEH, with IC values ranging from 14.24 to 46.35 µM. Additionally, the binding mechanism, key binding interactions, stability, and dynamic behaviour of the active compounds with the sEH enzyme were analysed using molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.
从肉豆蔻（Myristica fragrans）种子中分离得到了两种新的 neolignans，即 myrifralignans F-G（和），四种新的 diarylnonanoid 衍生物，即 myrifragranones A-D（-），以及 18 种已知化合物。使用电子圆二色性技术确定了这些次生代谢物的绝对构型。首次研究了这些分离化合物对可溶性环氧化物水解酶（sEH）的抑制潜力。其中，马巴利酮 B 和 C（和）以及四种新化合物——显示出对 sEH 的抑制活性，IC 值范围为 14.24 至 46.35 μM。此外，还使用分子对接和动力学模拟分析了活性化合物与 sEH 酶的结合机制、关键结合相互作用、稳定性和动态行为。我们的研究结果表明，肉豆蔻可能成为发现和开发新型 sEH 抑制剂的有前途的天然来源。
