海风藤化学成分及其抗菌活性和抗冠状病毒活性研究  

Chemical constituents and antibacterial,anti-coronavirus activities of Piperis Kadsurae Caulis

作　　者：林少丹 陈丽萍 潘永晨 熊秀比 李光盈 袁捷[1] 吴杰伟 LIN Shaodan;CHEN Liping;PAN Yongchen;XIONG Xiubi;LI Guangyi;YUAN Jie;WU Jiewei(School of Chinese Material Medica,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《中草药》2024年第15期5024-5032,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81903509);东莞广州中医药大学研究院培育项目(2023PY0102)。

摘　　要：目的研究海风藤(风藤Piperis kadsurae干燥藤茎)的化学成分,对其抗菌及抗冠状病毒进行活性评价。方法利用硅胶、Sephadex LH-20、MCI柱色谱以及半制备高效液相色谱等进行分离纯化,并运用NMR、HR-ESI-MS等技术对化合物进行结构鉴定。采用梯度稀释法,对分离所得的化合物进行抗蜡样芽胞杆菌、金黄色葡萄球菌以及耐甲氧西林金黄色球菌(MRSA)的活性评价,初步探讨了所分离化合物对SARS-CoV-2主蛋白酶(main protease,Mpro)的抑制活性。结果从海风藤醋酸乙酯萃取部位分离得到16个化合物,分别鉴定trans-2-methoxy-4.5-methylenedioxy-cinnamoy1-piperidide(1)、cis-2-methoxy-4.5-methylenedioxy-cinnamoy1-piperidide(2)、3-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-1-(1-piperidinyl)-2-propen-1-one(3)、4-[5-[(1E)-3-hydroxy-1-propen-1-yl]-7-methoxy-3-methyl-2-benzofuranyl]-2-methoxyphenol(4)、methyl(2E,4E)-5-(4-hydroxy-3-methoxyphenyl)-2,4-pentadienoate(5)、胡椒酸(6)、辛夷脂素(7)、denudatin B(8)、l-cinnamoylpyrrolidine(9)、假蒟亭碱(10)、胡椒碱(11)、胡椒新碱(12)、(E,E)-N-isobutyl-2,4-octadienamide(13)、4-allylbenzene-1,2-diol(14)、rabdosia acid A(15)、白桦脂酸(16)。与阳性对照药万古霉素相比,化合物1~2、4~10、12~16均具有显著的抗菌活性,其中,化合物1、5、6、10、12和15对金黄色葡萄球菌的最低抑菌浓度(minimum inhibitory concentration,MIC)值均为0.78μg/mL,化合物1~2、8~9、12和14对MRSA的MIC值均为3.12μg/mL。同时,与阳性抑制剂(Ebselen)相比,化合物2~4、8、11~12、14、16具有潜在的抗冠状病毒活性,半数抑制浓度(median inhibition concentration,IC_(50))为4~7μmol/L。结论化合物1~6为首次分离得到的天然产物,并首次提供化合物1~5的核磁数据;化合物15和16为首次从胡椒科植物中分离得到;化合物7、9~12、14为首次从海风藤植物中分离得到;化合物2、8、12在抗菌及抗冠状病毒方面均有较为显著的药理活性,可为后续研究和�Objective To study the chemical constituents of the Haifengteng(Piperis Kadsurae Caulis)(dried vine stems of P.kadsurae)and evaluate their antibacterial and anti-coronavirus activities.Methods The compounds were isolated and purified by silica gel,Sephadex LH-20,MCI column chromatography and semi-preparative high performance liquid chromatography,and their structures were identified by NMR and HR-ESI-MS and other spectral techniques.The activity of the isolated compounds against Bacillus cereus,Staphylococcus aureus and methicillin-resistant Staphylococcus aureus(MRSA)was evaluated by gradient dilution method.In addition,the inhibitory activity of the isolated compounds against SARS-CoV-2 main protease(Mpro)was preliminarily evaluated.Results A total of sixteen compounds were isolated and identified as trans-2-methoxy-4.5-methylenedioxy-cinnamoy1-piperidide(1),cis-2-methoxy-4.5-methylenedioxy-cinnamoy1-piperidide(2),3-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-1-(1-piperidinyl)-2-propen-1-one(3),4-[5-[(1E)-3-hydroxy-1-propen-1-yl]-7-methoxy-3-methyl-2-benzofuranyl]-2-methoxyphenol(4),methyl(2E,4E)-5-(4-hydroxy-3-methoxyphenyl)-2,4-pentadienoate(5),piperic acid(6),fargesin(7),denudatin B(8),1-cinnamoylpyrrolidine(9),sarmentine(10),piperine(11),piperanine(12),(E,E)-N-isobutyl-2,4-octadienamide(13),4-allylbenzene-1,2-diol(14),rabdosia acid A(15),betulinic acid(16).Compared with the positive control vancomycin,compounds 1—2、4—10、12—16 had significant antibacterial activity.The minimum inhibitory concentration(MIC)values of compounds 1,5,6,10,12 and 15 against Staphylococcus aureus were 0.78μg/mL,and the MIC values of compounds 1—2、8—9、12 and 14 against MRSA were 3.12μg/mL.At the same time,compounds 2—4,8,11—12,14 and 16 showed potential anti-coronavirus activity with median inhibition concentration(IC_(50))values ranging from 4—7μmol/L.Conclusion Compounds 1—6 were the natural products isolated for the first time,and the NMR data of compounds 1—5 were provided firstly in our study.Compounds 1

关 键 词：海风藤 酰胺类生物碱 抗耐甲氧西林金黄色球菌 抗冠状病毒 rabdosia acid A 白桦脂酸 胡椒新碱 

分 类 号：R284.1[医药卫生—中药学]