红茴香小分子化合物降尿酸活性及ADMET性质的分子对接
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摘要
目的明确红茴香降尿酸的活性成分及作用机制。方法通过检索相关文献建立红茴香已知小分子化合物配体库,从蛋白PDB数据库获得黄嘌呤氧化酶相关蛋白(1N5X,1FIQ)作为筛选降尿酸药物靶点,用Discovery Studio 3. 0(DS)中Lib Dock对接模块虚拟筛选黄嘌呤氧化酶抑制剂,用ADMET模块对药代动力学性质进行预测。结果红茴香中的黄酮苷类成分包括槲皮素-4'-O-β-D-葡萄糖苷、槲皮苷、芹菜素-6-O-β-D-芦丁糖苷等,与1N5X,1FIQ具有较高的对接分数和较为适合的ADMET性质。结论红茴香中黄酮苷类通过抑制黄嘌呤氧化酶活性具有降尿酸活性,可为进一步研究开发降尿酸药物提供参考。
Objective To make the material basis and mechanism of Illicium lanceolatum in lowering uric acid clear. Methods A molecular compound data bank of Illicium lanceolatum was established as ligand by searching the relevant literature. The three-dimensional crystal structure of xanthine oxidase( PDB code: 1 N5 X,1 FIQ) from Protein Data Bank was downloaded to be a target on selecting candidates of hyperuricemia. The molecular docking method was used to screen the inhibitors of xanthine oxidase from Illicium lanceolatum by Discovery Studio( DS 3. 0) LibDock. The pharmacokinetic properties were also predicted by Discovery Studio/ADMET. Results The flavone glycosides from Illicium lanceolatum,including quercetin-4'-O-β-D-glucoside,quercitrin and apigenin-6-O-β-D-lutinoside,show higher docking score with1 N5 X and 1 FIQ,and also have suitable ADMET properties. Conclusion The flavone glycosides from Illicium lanceolatum possess uric acid reduction activity by inhibition of xanthine oxidase,providing reference for further development of new drugs of hyperuricemia.
Objective To make the material basis and mechanism of Illicium lanceolatum in lowering uric acid clear. Methods A molecular compound data bank of Illicium lanceolatum was established as ligand by searching the relevant literature. The three-dimensional crystal structure of xanthine oxidase( PDB code: 1 N5 X,1 FIQ) from Protein Data Bank was downloaded to be a target on selecting candidates of hyperuricemia. The molecular docking method was used to screen the inhibitors of xanthine oxidase from Illicium lanceolatum by Discovery Studio( DS 3. 0) LibDock. The pharmacokinetic properties were also predicted by Discovery Studio/ADMET. Results The flavone glycosides from Illicium lanceolatum,including quercetin-4'-O-β-D-glucoside,quercitrin and apigenin-6-O-β-D-lutinoside,show higher docking score with1 N5 X and 1 FIQ,and also have suitable ADMET properties. Conclusion The flavone glycosides from Illicium lanceolatum possess uric acid reduction activity by inhibition of xanthine oxidase,providing reference for further development of new drugs of hyperuricemia.
引文
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[11]段磊.八角科植物果皮化学成分与促神经突起生长活性研究[D].北京:北京中医药大学,2005.
[12] XUAN G,GUOWEI W,NAIDAN Z,et al. New phenylpropanoid and other compounds from Illicium lanceolatum with inhibitory activities against LPS-induced NO production in RAW 264. 7 macrophages[J]. Fitoterapia,2014,95(10):51-57.
[13]刘慧,杨春澍.七种八角果实挥发油成分分析[J].中国科学院大学学报,1989,27(4):317-320.
[14] OKAMOTO K,EGER B T,NISHINO T,et al. An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition[J]. J Biol Chem,2003,278(3):1848-1855.
[15] ENROTH C,EGER B T,OKAMOTO K,et al. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase:Structure-based mechanism of conversion[J]. Proc Natl Acad Sci U S A,2000,97(20):10723-10728.
[16]王娜,刘会臣,侯艳宁.细胞色素P4502D6与药物代谢[J].中国临床药理学杂志,2001,17(4):308-312.
[17]陈晴,铁远,胡咏川,等.抗痛风相关的高尿酸血症药物的研究进展[J].中国临床药理学杂志,2017,33(9):853-856.
[2]中国科学院《中国植物志》编辑委员会.中国植物志[M].北京:科技出版社,1996:213-226.
[3]郑成.红茴香及红茴香注射剂指纹图谱的研究[D].杭州:浙江大学,2010.
[4]王国伟.披针叶茴香茎、叶的化学成分及抗炎活性研究[D].上海:第二军医大学,2012.
[5]梁婕.莽草的化学成分和生物活性研究[D].福州:福建中医药大学,2011.
[6]桂璇.红茴香根皮的化学成分及抗痛风性关节炎的活性研究[D].福州:福建中医药大学,2014.
[7]李慧娟,王丽霞,刘孟奇,等.披针叶茴香果实的化学成分研究[J].中国药学杂志,2014,49(8):636-639.
[8]李慧娟.披针叶茴香化学成分研究[D].郑州:郑州大学,2014.
[9] LIU J F,LI H J,WANG L X,et al. Two new monoterpenes from the fruits of Illicium lanceolatum[J]. Molecules,2013,18(10):11866-11872.
[10] KUBO M,NISHIKAWA Y,HARADA K,et al. Tetranorsesquiterpenoids and santalane-type sesquiterpenoids from Illicium lanceolatum and their antimicrobial activity against the oral pathogen porphyromonas gingivalis[J]. J Nat Prod,2015,78(6):1466-1469.
[11]段磊.八角科植物果皮化学成分与促神经突起生长活性研究[D].北京:北京中医药大学,2005.
[12] XUAN G,GUOWEI W,NAIDAN Z,et al. New phenylpropanoid and other compounds from Illicium lanceolatum with inhibitory activities against LPS-induced NO production in RAW 264. 7 macrophages[J]. Fitoterapia,2014,95(10):51-57.
[13]刘慧,杨春澍.七种八角果实挥发油成分分析[J].中国科学院大学学报,1989,27(4):317-320.
[14] OKAMOTO K,EGER B T,NISHINO T,et al. An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition[J]. J Biol Chem,2003,278(3):1848-1855.
[15] ENROTH C,EGER B T,OKAMOTO K,et al. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase:Structure-based mechanism of conversion[J]. Proc Natl Acad Sci U S A,2000,97(20):10723-10728.
[16]王娜,刘会臣,侯艳宁.细胞色素P4502D6与药物代谢[J].中国临床药理学杂志,2001,17(4):308-312.
[17]陈晴,铁远,胡咏川,等.抗痛风相关的高尿酸血症药物的研究进展[J].中国临床药理学杂志,2017,33(9):853-856.