Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceutical, Zhejiang University of Technology, Hangzhou, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Eur J Med Chem. 2019 Oct 15;180:367-382. doi: 10.1016/j.ejmech.2019.07.031. Epub 2019 Jul 12.
A series of hybrids of hydroxypyridinone and coumarin were rationally designed, synthesized and biologically evaluated for their iron ion chelating and MAO-B inhibitory activities. Most of the compounds displayed excellent iron ion chelating effects and moderate to good anti-MAO-B activities. Compound 27a exhibited the most potent activity against MAO-B, with an IC value of 14.7 nM. Importantly, 27a showed good U251 cell protective effect and significantly ameliorated the cognitive dysfunction of scopolamine-induced AD mice. Moreover, molecular docking was performed to elucidate the probable ligand-receptor interaction, and the structure-activity relationships were also summarized.
一系列羟基吡啶酮和香豆素的杂合体被合理设计、合成并进行了铁离子螯合和 MAO-B 抑制活性的生物评价。大多数化合物表现出优异的铁离子螯合作用和中等至良好的抗 MAO-B 活性。化合物 27a 对 MAO-B 的抑制活性最强，IC 值为 14.7 nM。重要的是，27a 对 U251 细胞具有良好的保护作用，显著改善了东莨菪碱诱导的 AD 小鼠的认知功能障碍。此外，还进行了分子对接以阐明可能的配体-受体相互作用，并总结了构效关系。
