[1] ZHOU Yaobin GAO Dongmei WANG Yifeng WANG Ting GAO Yufei ZHANG Meiqian WANG Chuan ZHOU Jing,.Evaluation of Vasodilatory Activity and Molecular Docking Simulation of Wuzhuyu Alkaloid Derivatives [J]. Journal of Shaanxi University of Traditional Chinese Medicine, 2024, (05): 91-96. [doi: 10.13424/j.cnki.jsctcm.2024.05.015]
Evaluation of Vasodilatory Activity and Molecular Docking Simulation of Wuzhuyu Alkaloid Derivatives
- Article number:
- 2096-1340(2024)05-0091-06
- Keywords:
- Key words： Derivative of rutaecarpa alkaloids; Cytotoxicity; Vasodilatory activity; Molecular docking
- ZTFLH:
- R285
- Code:
- A
- Abstract:
- Abstract： Objective To investigate the cytotoxicity,vasodilatory activity,and mechanism of action of a novel derivative of rutaecarpa alkaloids.Methods Six derivatives of rutaecarpa alkaloids were synthesized and their vasodilation function was tested by vascular ring assay.The cytotoxicity of the compounds was evaluated by CCK-8 cell proliferation assay and endothelial cell toxicity assay.Select compounds with high activity,use AutoDock software for molecular docking,and analyze the interaction mode with eNOS enzyme.Results Six derivatives of rutaecarpa alkaloids were synthesized,and their vasodilation function was evaluated.The results showed that all derivatives of rutaecarpa alkaloids had a vasodilatory effect on the mesenteric arteries of rats pre contracted with phenylephrine,with derivative 4c of rutaecarpa alkaloids having the strongest vasodilatory effect.The cytotoxicity evaluation showed that compounds 4b,4e,and 4f in the derivatives of Evodia rutaecarpa alkaloids had slightly lower inhibition rates on liver cancer cells,and the cytotoxicity was slightly reduced compared to the original drug;The cytotoxicity of compound 4a is comparable to that of the original drug,while the cytotoxicity of compounds 4c and 4d is slightly higher than that of the original drug.The results of endothelial cell survival assay showed that compound 4c had similar toxicity to the original drug on endothelial cells.The molecular docking results showed that compounds with higher activity have good energy matching with eNOS enzyme,and form hydrogen bonds with the active amino acid residues of the protein.The ligand has good binding ability with the receptor.Conclusion The molecular docking results are consistent with the experimental results of activity determination.These derivatives of rutaecarpa alkaloids are likely to have good vasodilation ability by activating the activity of eNOS enzyme.
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Memo
基金项目：国家自然科学基金项目（22201169）；陕西省科技厅青年基金项目（2021JQ-723）；陕西省教育厅专项基金项目(21JK0601）；国家级大创项目（202110716025）