咖啡酸的化学改性及产物抗氧化性的研究
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摘要
以咖啡酸和氨基酸乙酯盐酸盐为原料,1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)及1-羟基苯并三唑(HOBt)为催化剂,合成咖啡酰甘氨酸乙酯、咖啡酰丙氨酸乙酯、咖啡酰丝氨酸乙酯、咖啡酰苏氨酸乙酯4种产物。利用核磁共振氢谱(~1H NMR)和高效液相色谱-质谱(HPLC-MS)对产物结构进行表征,考察了咖啡酸化学改性产物对DPPH自由基及羟基自由基活性的抑制率及对红细胞膜的刺激性,并与咖啡酸单体进行了比较。结果表明,通过在咖啡酸中引入甘氨酸乙酯、丙氨酸乙酯、丝氨酸乙酯和苏氨酸乙酯后,4种咖啡酸酰胺类产物均呈现较好的抑制DPPH自由基、羟基自由基活性的效果;咖啡酰丝氨酸乙酯清除DPPH自由基能力较强,其IC_(50)值为13.5 μmol/L;咖啡酰丙氨酸乙酯清除羟基自由基能力较强,其IC_(50)值为0.214 mmol/L。红细胞溶血试验结果表明,4种咖啡酸酰胺类衍生物的红细胞溶血率均低于咖啡酸单体。
Caffeoyl glycine ethyl ester, caffeoyl alanine ethyl ester, caffeoyl serine ethyl ester and caffeoyl threonine ethyl ester were synthesized from L-amino acid ethyl ester hydrochloride with caffeic acid in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC) and 1-hydroxybenzotriazole(HOBt). The structure of the products after the reaction was characterized by ~1H NMR and HPLC-MS. The inhibitory rates against DPPH radical and hydroxyl radical and the erythrocyte membrane irritation were investigated for the chemically modified products of caffeic acid which were compared with caffeic acid. The results show that all these four caffeic acid amide derivatives show good inhibition against DPPH radicals and hydroxyl radicals, which have introduced glycine ethyl ester, alanine ethyl ester, serine ethyl ester, and threonine ethyl ester in the molecular structure of caffeic acid. The caffeic acid amide derived from serine ethyl ester has the strongest scavenging activity against DPPH free radicals(IC_(50)=13.5 μmol/L), while the one derived from alanine ethyl ester is the strongest in scavenging hydroxyl radicals with an IC_(50) value of 0.214 mmol/L. The results of red blood cell hemolysis show that all these four caffeic acid amide derivatives exihibit lower hemolysis ratios than caffeic acid.
Caffeoyl glycine ethyl ester, caffeoyl alanine ethyl ester, caffeoyl serine ethyl ester and caffeoyl threonine ethyl ester were synthesized from L-amino acid ethyl ester hydrochloride with caffeic acid in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC) and 1-hydroxybenzotriazole(HOBt). The structure of the products after the reaction was characterized by ~1H NMR and HPLC-MS. The inhibitory rates against DPPH radical and hydroxyl radical and the erythrocyte membrane irritation were investigated for the chemically modified products of caffeic acid which were compared with caffeic acid. The results show that all these four caffeic acid amide derivatives show good inhibition against DPPH radicals and hydroxyl radicals, which have introduced glycine ethyl ester, alanine ethyl ester, serine ethyl ester, and threonine ethyl ester in the molecular structure of caffeic acid. The caffeic acid amide derived from serine ethyl ester has the strongest scavenging activity against DPPH free radicals(IC_(50)=13.5 μmol/L), while the one derived from alanine ethyl ester is the strongest in scavenging hydroxyl radicals with an IC_(50) value of 0.214 mmol/L. The results of red blood cell hemolysis show that all these four caffeic acid amide derivatives exihibit lower hemolysis ratios than caffeic acid.
引文
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[3]Mattila P.Phenolic acids in berries,fruits,and beverages[J].Journal of Agricultural and Food Chemistry,2006,54(19):7193-7199.
[4]Sun Y,Yu Y Y,Cao S W.Antioxidant capacity of caffeic acid,phloretin and glutathione mixtures and formula optimization[J].Asian Journal of Chemistry,2013,25(7):3971-3978.
[5]Marquez,Sancho N,Macho R,et al.Caffeic acid phenethyl ester inhibits T-cell activation by targeting both nuclear factor of activated T-cells and NF-kappaB transcription factors[J].Journal of Pharmacology&Experimental Therapeutics,2004,308(3):993-1001.
[6]Fan Jinbo,Cai Qiantong,Feng Xuqiao,et al.Study on antioxidant activity of caffeic acid in vitro[J].Journal of Chinese Institute of Food Science and Technology,2015,15(3):65-73.
[7]Pietta P G.Flavonoids as antioxidant[J].Journal of Natural Products,2000,63(7):1035-1042.
[8]Lu Liang.The protective effect of phenethyl caffeate on free radicalinduced oxidative hemolysis and lipid peroxidation injury[D].Lanzhou:Lanzhou University,2007.
[9]Son S,Lewis B A.Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues:structure-activity relationship[J].Journal of Agricultural&Food Chemistry,2002,50(3):468-472.
[10]Sun Haoyi,Hao Baoyan,Zhang Haochao,et al.Research situation of caffeic acid[J].Food and Drug,2017,19(2):151-152.
[11]Wei Q Y,Jiang H,Zhang J X,et al.Synthesis of N-hydroxycinnamoyl amino acid ester analogues and their free radical scavenging and antioxidative activities[J].Medicinal Chemistry Research,2012,21(8):1905-1911.
[12]Jiang R W,Lau K M,Hon P M,et al.Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza[J].Current Medicinal Chemistry,2005,12(2):237-246.
[13]Yoo Y J,Dong H N,Jung S Y,et al.Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2011,21(10):2850-2854.
[14]Aladedunye F.Novel caffeic acid amide antioxidants:Synthesis,radical scavenging activity and performance under storage and frying conditions[J].Food Chemistry,2012,130(4):945-952.
[15]Anselmi C,Centini M,Andreassi M,et al.Conformational analysis:a tool for the elucidation of the antioxidant properties of ferulic acid derivatives in membrane models[J].Journal of Pharmaceutical&Biomedical Analysis,2004,35(5):1241-1249.
[16]Fan Q,Jiang H,Yuan E D,et al.Tyrosinase inhibitory effects and antioxidative activities of novel cinnamoyl amides with amino acid ester moiety[J].Food Chemistry,2012,134(2):1081-1087.