Hou Ya-Jing, Wang Cheng, Wang Tao, Huang Li-Min, Lin Yuan-Yuan, He Huai-Zhen
a School of Pharmacy , Xi'an Jiaotong University , Xi'an 710061 , China.
b Department of Food , Xi'an Institute for Food and Drug Control , Xi'an 710054 , China.
J Asian Nat Prod Res. 2019 Jan;21(1):43-50. doi: 10.1080/10286020.2017.1391228. Epub 2017 Oct 30.
Two series of imperatorin analogs were synthesized based on our previous research and evaluated for their vasodilatation activities on in vitro rat mesenteric artery, basilar artery, and renal artery ring models. Target compounds were characterized by infrared, H NMR, and mass spectra. Most derivatives possessed significant vasodilatory activity on the mesenteric artery, and compound 3a exhibited favorable and broad vasodilatation activities on three kinds of rat artery ring models. The pharmacological results indicated that introducing nitrogen-contained ring in side chain or large steric hindrance at the distal end could increase the vasodilatory activity. Further, replacement of oxygen atom (-O-) in the skeleton of furocoumarin derivatives with nitrogen (-NH-) could cause the decrease of vasodilatory activity. The molecular docking also indicated that compound 3a showed a best affinity with α-1C receptor (PDB ID: 3G43). All these results suggested compound 3a would be a potential vasodilatory agent for hypertension.
基于我们之前的研究合成了两系列欧前胡素类似物，并在体外大鼠肠系膜动脉、基底动脉和肾动脉环模型上评估了它们的血管舒张活性。目标化合物通过红外光谱、氢核磁共振光谱和质谱进行表征。大多数衍生物对肠系膜动脉具有显著的血管舒张活性，化合物3a在三种大鼠动脉环模型上表现出良好且广泛的血管舒张活性。药理结果表明，在侧链引入含氮环或在远端引入大的空间位阻可增加血管舒张活性。此外，用氮（-NH-）取代呋喃香豆素衍生物骨架中的氧原子（-O-）会导致血管舒张活性降低。分子对接还表明化合物3a与α-1C受体（PDB ID：3G43）表现出最佳亲和力。所有这些结果表明化合物3a可能是一种用于治疗高血压的潜在血管舒张剂。
