1-（5'-溴阿魏酰基）-4-苄基哌嗪盐酸盐类似物的合成及药理研究
|
摘要
阿魏酸属于酚类抗氧化药物,阿魏酸衍生物具有抗氧化、抗炎、抑制血小板聚集、降血糖、抗肿瘤、抗辐射等药理作用。本研究对阿魏酸进行结构改造,保留阿魏酸的酚羟基这一抗氧化药效基团,将其羧基改造成酰胺,设计合成一系列1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物,并初步测定其药理活性。
一、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的合成
目的:合成1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物
方法:经苯环溴代、Knoevenagel缩合反应合成5'-溴阿魏酸,再经酚羟基乙酰化、羧酸卤置换、N-酰化、脱乙酰基后得到1-(5'-溴阿魏酰基)-4-苄基哌嗪,最后与盐酸成盐得到目标化合物。
结果:合成9个新化合物,为1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物,均通过元素分析、MS、1HNMR、IR结构鉴定。
结论:找到一条合成1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的路线。
二、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物体外清除羟自由基活性研究
目的:研究1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物在体外清除羟自由基(?OH)的活性。方法:采用邻二氮菲-Fe2+氧化法测定1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物、阿魏酸(FA)和抗坏血酸(Vc)在体外对Fenton反应产生?OH的清除能力,计算表观清除率(CL),采用SNK检验比较各药物最大?OH表观清除率(CLmax)的差异。
结果:9个目标化合物均具有不同程度的体外清除?OH活性,且都有明显量效关系。L5的CLmax最大,L8的CLmax最小,L1、L3、L5、L7的CLmax都比FA和Vc大,L1、L3、L5、L6、L7的CLmax都比Vc大。
结论:目标化合物均具有体外清除?OH活性,苄基苯环上取代基的类型和取代位置影响目标化合物均体外清除?OH的活性。苄基苯环上2-Cl、3-Cl、2-CH3、4-CH3、3-OCH3取代,可增强体外清除?OH活性;3-CH3取代,体外清除?OH活性基本不变;2-OCH3、4-OCH3取代,体外清除?OH活性降低。
三、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物抑制小鼠耳肿胀活性研究
目的:研究1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的抗炎活性。
方法:目标化合物L5、阿魏酸、布洛芬配制成混悬剂,通过计算肿胀度和肿胀抑制率评价它们抑制巴豆油混合液所致小鼠耳肿胀的作用,运用Dunnett双侧检验比较各给药组与空白组肿胀度的差异,采用SNK检验比较各给药组间肿胀抑制率的差异。
结果:目标化合物L5、阿魏酸、布洛芬在各剂量都有极显著的抑制小鼠耳肿胀作用。各剂量肿胀抑制率的大小顺序为:100mg/kg,布洛芬>阿魏酸>L5;200mg/kg,布洛芬>L5>阿魏酸;400mg/kg,L5≈阿魏酸>布洛芬。
结论:目标化合物L5、阿魏酸、布洛芬在各剂量都有抗炎活性。
Ferulic acid is a phenolic anti-oxidant. Ferulic acid derivatives have the pharmacology activities of anti-oxidation, anti-inflammatory, inhibiting thrombocyte congregation, lowering blood sugar, anti-tumor, radiation inhibition. In our study, we modificated the structure of ferulic acid. The carboxylic acid was transformed into amide while the phenolic hydroxyl group was reserved to keep its anti-oxidation activity. A series of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthesized, and their pharmacology activities were evaluated.
1. Synthesis of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs
Objective: To synthesize 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: 5'-bromo ferulic acid was synthesized through bromo substitute and Knoevenagel reaction.1-(5'-bromo feruloyl)-4-benzyl piperazine was prepared via acetylation of phenolic hydroxyl, oxalyl chloride exchange with acid, N-acylation, removing of acetyl.Finally the target compounds were synthesized by 1-(5'-bromo feruloyl)-4-benzyl piperazine salification with hydrochloric acid.
Results: 9 novel 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthe- sized. Their structures were identified by elemental analysis, 1HNMR, MS and IR.
Conclusion: A synthesis route to prepare 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochlor- ide analogs was established.
2. Hydroxyl radical scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs
Objective: To study hydroxyl radical(?OH) scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: The ?OH scavenging activities in vitro of target compounds,ferulic acid(FA) and L-ascorbic acid(Vc) were analysed through 1,10-phenanthroline-Fe2+ detection system. Then the ?OH clearance percentage(CL) were calculated. The ?OH maximum clearance percentage(CLmax) differences between the drugs were analysed by SNK test.
Results: All target compounds showed marked ?OH scavenging activities in vitro and had obvious dose-effect relationships. L5 had the highest CLmax. L8 had the lowest CLmax. L1, L3, L5 and L7 had higher CLmax than FA and Vc. L1, L3, L5, L6 and L7 had higher CLmax than Vc.
Conclusion: All target compounds showed marked ?OH scavenging activities in vitro. The activity was influenced by the type and location of the substitute on benzal benzene ring. 2-Cl, 3-Cl, 2-CH3, 4-CH3 and 3-OCH3 enhanced the activity. 3-CH3 did not change the activity. 2-OCH3 and 4-OCH3 reduced the activity.
3. Ear swelling inhibition activities in rats of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs Objective: To study anti-inflammatory activities of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: L5, ferulic acid and ibuprofen were prepared as suspensions. Swelling degrees and swelling inhibitions were calculated to evaluate the ear swelling inhibition in rats induced by croton oil mixture. The swelling degree differences between the drug groups and control were analysed by two side Dunnett test. The swelling inhibition differences between the drug groups were analysed by SNK test. Results: All measuring doses of L5,ferulic acid and ibuprofen had extremely marked ear swelling inhibition activities in rats. The sequences of swelling inhibition at each doses were the following. 100mg/kg, ibuprofen>ferulic acid>L5.200mg/kg, ibuprofen>L5>ferulic acid. 400mg/kg, L5≈ferulic acid>ibuprofen.
Conclusion: All measuring doses of L5, ferulic acid and ibuprofen had anti-inflammatory activities.
一、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的合成
目的:合成1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物
方法:经苯环溴代、Knoevenagel缩合反应合成5'-溴阿魏酸,再经酚羟基乙酰化、羧酸卤置换、N-酰化、脱乙酰基后得到1-(5'-溴阿魏酰基)-4-苄基哌嗪,最后与盐酸成盐得到目标化合物。
结果:合成9个新化合物,为1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物,均通过元素分析、MS、1HNMR、IR结构鉴定。
结论:找到一条合成1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的路线。
二、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物体外清除羟自由基活性研究
目的:研究1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物在体外清除羟自由基(?OH)的活性。方法:采用邻二氮菲-Fe2+氧化法测定1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物、阿魏酸(FA)和抗坏血酸(Vc)在体外对Fenton反应产生?OH的清除能力,计算表观清除率(CL),采用SNK检验比较各药物最大?OH表观清除率(CLmax)的差异。
结果:9个目标化合物均具有不同程度的体外清除?OH活性,且都有明显量效关系。L5的CLmax最大,L8的CLmax最小,L1、L3、L5、L7的CLmax都比FA和Vc大,L1、L3、L5、L6、L7的CLmax都比Vc大。
结论:目标化合物均具有体外清除?OH活性,苄基苯环上取代基的类型和取代位置影响目标化合物均体外清除?OH的活性。苄基苯环上2-Cl、3-Cl、2-CH3、4-CH3、3-OCH3取代,可增强体外清除?OH活性;3-CH3取代,体外清除?OH活性基本不变;2-OCH3、4-OCH3取代,体外清除?OH活性降低。
三、1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物抑制小鼠耳肿胀活性研究
目的:研究1-(5'-溴阿魏酰基)-4-苄基哌嗪盐酸盐类似物的抗炎活性。
方法:目标化合物L5、阿魏酸、布洛芬配制成混悬剂,通过计算肿胀度和肿胀抑制率评价它们抑制巴豆油混合液所致小鼠耳肿胀的作用,运用Dunnett双侧检验比较各给药组与空白组肿胀度的差异,采用SNK检验比较各给药组间肿胀抑制率的差异。
结果:目标化合物L5、阿魏酸、布洛芬在各剂量都有极显著的抑制小鼠耳肿胀作用。各剂量肿胀抑制率的大小顺序为:100mg/kg,布洛芬>阿魏酸>L5;200mg/kg,布洛芬>L5>阿魏酸;400mg/kg,L5≈阿魏酸>布洛芬。
结论:目标化合物L5、阿魏酸、布洛芬在各剂量都有抗炎活性。
Ferulic acid is a phenolic anti-oxidant. Ferulic acid derivatives have the pharmacology activities of anti-oxidation, anti-inflammatory, inhibiting thrombocyte congregation, lowering blood sugar, anti-tumor, radiation inhibition. In our study, we modificated the structure of ferulic acid. The carboxylic acid was transformed into amide while the phenolic hydroxyl group was reserved to keep its anti-oxidation activity. A series of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthesized, and their pharmacology activities were evaluated.
1. Synthesis of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs
Objective: To synthesize 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: 5'-bromo ferulic acid was synthesized through bromo substitute and Knoevenagel reaction.1-(5'-bromo feruloyl)-4-benzyl piperazine was prepared via acetylation of phenolic hydroxyl, oxalyl chloride exchange with acid, N-acylation, removing of acetyl.Finally the target compounds were synthesized by 1-(5'-bromo feruloyl)-4-benzyl piperazine salification with hydrochloric acid.
Results: 9 novel 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthe- sized. Their structures were identified by elemental analysis, 1HNMR, MS and IR.
Conclusion: A synthesis route to prepare 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochlor- ide analogs was established.
2. Hydroxyl radical scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs
Objective: To study hydroxyl radical(?OH) scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: The ?OH scavenging activities in vitro of target compounds,ferulic acid(FA) and L-ascorbic acid(Vc) were analysed through 1,10-phenanthroline-Fe2+ detection system. Then the ?OH clearance percentage(CL) were calculated. The ?OH maximum clearance percentage(CLmax) differences between the drugs were analysed by SNK test.
Results: All target compounds showed marked ?OH scavenging activities in vitro and had obvious dose-effect relationships. L5 had the highest CLmax. L8 had the lowest CLmax. L1, L3, L5 and L7 had higher CLmax than FA and Vc. L1, L3, L5, L6 and L7 had higher CLmax than Vc.
Conclusion: All target compounds showed marked ?OH scavenging activities in vitro. The activity was influenced by the type and location of the substitute on benzal benzene ring. 2-Cl, 3-Cl, 2-CH3, 4-CH3 and 3-OCH3 enhanced the activity. 3-CH3 did not change the activity. 2-OCH3 and 4-OCH3 reduced the activity.
3. Ear swelling inhibition activities in rats of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs Objective: To study anti-inflammatory activities of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.
Methods: L5, ferulic acid and ibuprofen were prepared as suspensions. Swelling degrees and swelling inhibitions were calculated to evaluate the ear swelling inhibition in rats induced by croton oil mixture. The swelling degree differences between the drug groups and control were analysed by two side Dunnett test. The swelling inhibition differences between the drug groups were analysed by SNK test. Results: All measuring doses of L5,ferulic acid and ibuprofen had extremely marked ear swelling inhibition activities in rats. The sequences of swelling inhibition at each doses were the following. 100mg/kg, ibuprofen>ferulic acid>L5.200mg/kg, ibuprofen>L5>ferulic acid. 400mg/kg, L5≈ferulic acid>ibuprofen.
Conclusion: All measuring doses of L5, ferulic acid and ibuprofen had anti-inflammatory activities.
引文
[1]. Lu G.H., Chan K., Leung K., et al. Assay of free ferulic acid and total ferulic acid for quality assessment of Angelica sinensis[J]. Journal of Chromatograph A, 2005, 1068: 209–219.
[2]. Ou S., Luo Y., Xue F., et al. Seperation and purification of ferulic acid in alkaline- hydrolysate from sugarcane bagasse by activated charcoal adsorption/anion macro-porous resin exchange chromatography[J]. Journal of Food Engineering, 2007, 78 (4): 1298-1304.
[3].唐灵芝. 1-阿魏酰基-4-苄基哌嗪盐酸盐类似物的合成及体外清除羟自由基活性研究.汕头大学硕士学位论文. 2004. 20-51.
[4]. Prasad N.R., Samivel R., Kodukkur V.P., et al. Ferulic acid inhibits UV-B–induced oxidative stress in human lymphocytes[J]. Nutrition Research, 2007, 27: 559–564.
[5]. Nomura E., Hosoda A., Morishita H., et al. Synthesis of novel polyphenols consisted of ferulic and gallic acids,and their inhibitory effects on phorbol ester-induced Epstein–Barr virus activation and superoxide generation[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1069–1075.
[6]. Shinya S., Hiroshi O., Katsuhisa N., et al. Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, raw 264.7[J]. Cytokine, 1997, 9(4): 242-248.
[7].杨柳,吴本俨,顾瑛,等.阿魏酸钠治疗缺血性结肠炎的研究[J].中国新药杂志, 2007, 16(24): 2024-2026.
[8].胡益勇,徐晓玉.阿魏酸的化学和药理研究进展[J].中成药, 2006, 28(2): 253-254.
[9]. Surinder K.Y., Arunachalam G., Subramanian S., et al. Synergistic salubrious effect of ferulic acid and ascorbic acid on membrane-bound phosphatases and lysosomal hydrolases during experimental myocardial infaration in rats[J]. Life Sciences, 2006, 80: 258–263.
[10]. Nomura E., Kashiwada A., Hosoda A, et al. Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro[J]. Bioorganic and Medicinal Chemistry, 2003, 11: 3807–3813.
[11]. Atsuyo F., Hideyuki S., Asako D., et al. Ferulic acid prevents pathological and functionalabnormalities of the kidney in Otsuka Long-Evans Tokushima fatty diabetic rats[J]. Diabetes Research and Clinical Practice, 2008, 79: 11–17.
[12]. Wang T., Chen L.X., Long Y., et al. DNA damage induced by caffeic acid phenyl ester in the presence of Cu(II) ions:Potential mechanism of its anticancer properties[J]. Cancer Letter, 2008, doi: 10.1016/j. canlet. 2007. 12. 021.
[13]. Gururaj J., Marzia P., Rukhsana S., et al. In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE)from oxidative stress mediated by 2,2-azobis(2-amidino-propane) dihydrochloride (AAPH) or Fe2+/H2O2:Insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders[J]. Neurochemistry International, 2006, 48: 318-327.
[14]. Adluri R.S., Shanmugavel M., Nagarajan D., et al. Influence of ferulic acid on nicotine- induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine[J]. Toxicology, 2008, 243: 317-329.
[15]. Yang F., Zhou B.R., Zhang P., et al. Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis[J]. Chemico-Biological Interactions, 2007, 170: 231–243.
[16]. Yu L., Zhang Y., Ma R., et al. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain[J]. European Neuropsychopharmacology, 2006, 16: 170- 177.
[17]. Srinivasan M., Ram A.S., K.Raveendran P., et al. Influence of ferulic acid onγ-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes[J]. Toxicology, 2006, 228: 249–258.
[18].黄华永,沈海星,郑锦鸿.阿魏酸及其类似物的合成及其清除自由基活性研究[J].中国新药杂志, 2006, 15(6): 454-457.
[19]. Nomura E., Hosoda A., Morishita H., et al. Synthesis of novel polyphenols consisted of ferulic and gallic acids, and their inhibitory effects on phorbol ester-induced Epstein–Barr virus activation and superoxide generation[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1069–1075.
[20].刘鹰翔,计志忠,牟孝硕,等. (E)-4-芳酰氧基苯丙烯酸类衍生物的合成及抑癌活性[J].Journal of Chinese Pharmaceutical Sciences, 2002, 11(3): 73-77.
[21].刘鹰翔,计志忠,牟孝硕,等. (E)-4-酰氧基苯丙烯酸类衍生物的合成及抑癌活性[J].中国药物化学杂志, 2001, 11(2): 76-79.
[22].马玉卓,刘鹰翔.肉桂酰异阿魏酸的合成[J].广东药学, 2002, 12(4): 4-5.
[23]. Hosoda A., Ozaki Y., Kashiwada A., et al. Syntheses of ferulic acid derivatives and their suppressive effects on cyclooxygenase-2 promoter activity[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1189–1196.
[24]. Wang X., Salomon S., Phillip D., et al. Cytoprotective effect of caffeic acid phenethyl ester (CAPE) and catechol ring-fluorinated CAPE derivatives against menadione-induced oxidative stress in human endothelial cells[J]. Bioorganic and Medicinal Chemistry, 2006, 14: 4879–4887.
[25]. Moriyasu T., Tatsuji S., Tomoyuki F., et al. Esterification of ferulic acid with polyols using a ferulic acid esterase from Aspergillus niger[J]. Biochimica and Biophysica Acta, 2006, 1760: 1071–1079.
[26].刘鹰翔,汪金平,计志忠,等. 1-取代-2-(3-甲氧基-4-肉桂酰氧基)苯乙烯衍生物的合成及抗血小板聚集活性[J].中国药物化学杂志, 1996, 6(2): 79-84.
[27].刘鹰翔,马玉卓,江涛,等. (E)-4-芳酰氧基苯基丁烯-3-酮-2衍生物的合成及生物活性[J].中国药物化学杂志, 2000, 10(4): 242-245.
[28]. Nomura E., Kashiwada A., Hosoda A., et al. Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro[J]. Bioorganic and Medicinal Chemistry, 2003, 11: 3807–3813.
[29].刘鹰翔,马玉卓,计志忠,等. (E)-4-桂皮酰氧基苯乙烯衍生物的合成及抗炎活性[J].中国药物化学杂志, 1999, 9(3): 186-191.
[30]. Amselmi C., Centini M., Maggiore M., et al. Non-covalent inclusion of ferulic acid withα-cyclodextrin improves photo-stability and delivery:NMR and modeling studies[J]. Journal of Pharmaceutical and Biomedical Analysis, 2008, 46: 645–652.
[31]. Amselmi C., Centini M., Ricci M., et al. Analytical characterization of a ferulic acid/γ- cyclodextrin inclusion complex[J]. Journal of Pharmaceutical and Biomedical Analysis, 2006, 40: 875–881.
[32]. Rakotondramanana D.L.A., Melanie D., Michel B., et al. Synthesis of ferulic ester dimers,functionalisation and biological evaluation as potential antiatherogenic and antiplasmodial agents[J]. Bioorganic and Medicinal Chemistry, 2007, 15: 6018–6026.
[33]. Bernhard H.M., Brian L.H., Arjun R., et al. Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases[J]. Bioorganic and Medicinal Chemistry, 2006, 14: 7988–7998.
[34].闫雪梅,赵慧萍,严红.HPLC法测定通脉颗粒中阿魏酸的含量[J].中草药, 2003, 34(3): 230-231.
[35].宋金春,唐开勇.通脉口服液的质量标准研究[J].中国药房, 2006, 17(22): 1730-1732.
[36].运委,孙仲葆,刘戎.高效液相色谱法测定当归苦参丸中阿魏酸的含量[J].中国医院药学杂志, 2007, 27(10): 1477-1478.
[37].辛嘉英,郑妍,赵冠里,等.阿魏酸衍生物的应用及合成[J].化学世界, 2006, 5: 305- 306.
[38].吕以仙,陆阳,邓键等.有机化学.第6版[M].北京:人民卫生出版社,2004. 76-78.
[39].闻韧.药物合成反应.第2版[M].北京:化学工业出版社,2003. 213-216.
[40]. Hosoda A., Nomura E., Mizuno K., et al. Synthesis of feruloyl-myo-insitol derivatives and their inhibitory effects on phorbol ester-induced superoxide generation and esptein–barr virus activation[J]. Bioorganic and Medicinal Chemistry, 2002, 10(6): 1855–1863.
[41]. Hosoda A., Nomura E., Mizuno K., et al. Preparation of a(±)-1,6-Di-O-feruloyl-myo- inositol derivative: an efficient method for introduction of ferulic acid to 1,6-vicinal hydroxyl groups of myo-Inositol[J]. Journal of Organic Chemistry, 2001, 66: 7201.
[42].容国斌,朱士正.波谱数据表—有机化合物的结构解析.第2版[M].上海:华东理工大学出版社,2002. 164-367.
[43].宁永成.有机化合物结构鉴定与有机波谱学[M].北京:科学出版社,2000. 36-335.
[44].庞战军,周玟,陈瑗.自由基医学研究方法[M].北京:人民卫生出版社,2000. 14-15.
[45]. Zhao G., Xiang Z., Ye T., et al. Antioxidant activities of Salvia miltiorrhiza and Panax notoginseng[J]. Food Chemistry, 2006, 99: 767–774.
[46]. Lee C., Yoon J. Temperature dependence of hydroxyl radical formation in the hv/ Fe3+/H2O2 and Fe2+/H2O2 systems[J]. Chemosphere, 2004, 56: 923-934.
[47].李甘地,来茂德,杨光华等.病理学[M].北京:人民卫生出版社,2002. 81-82.
[48].李端,殷明,任雷鸣,等.药理学.第5版[M].北京:人民卫生出版社,2006. 166-173.
[49].赵一玫,夏丹,艾彩萍,等.布洛芬衍生物的合成及抗炎活性[J].中国药物化学杂志, 2005, 15(6): 360-362.
[50]. Zhang B., He X.L., Ding Y., et al. Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: Towards a better non-steroidal anti-inflammatory drug[J]. European Journal of Pharmacology, 2006, 530: 166-171.
[51].徐叔云,卞如濂,陈修等.药理实验方法学.第3版[M].北京:人民卫生出版社, 2002. 905-911.
[52]. Sander H., Anita H., Annemarie S., et al. Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice[J]. European Journal of Pharmacology, 2006, 531: 264–269.
[53]. Ramy R. H., Ashraf B.A., Amani E. K., et al. Anti-inflammatory effects of jojoba liquid wax in experimental models[J]. Pharmacological Research, 2005, 51: 95–105.
[54].邹移海,徐志伟,苏钢强等.实验动物学[M].北京:科学出版社,2004. 176-182.
[55].金丕焕,曹素华.医用统计方法[M].上海:复旦大学出版社,2002. 64-68.
[56]. Mavar-Manga H., Haddad M., Pieters L., et al. Anti-inflammatory compounds from leaves and root bark of Alchornea cordifolia (Schumach. and Thonn.) Mull. Arg.[J]. Journal of Ethnopharmacology, 2008, 115: 25–29.
[2]. Ou S., Luo Y., Xue F., et al. Seperation and purification of ferulic acid in alkaline- hydrolysate from sugarcane bagasse by activated charcoal adsorption/anion macro-porous resin exchange chromatography[J]. Journal of Food Engineering, 2007, 78 (4): 1298-1304.
[3].唐灵芝. 1-阿魏酰基-4-苄基哌嗪盐酸盐类似物的合成及体外清除羟自由基活性研究.汕头大学硕士学位论文. 2004. 20-51.
[4]. Prasad N.R., Samivel R., Kodukkur V.P., et al. Ferulic acid inhibits UV-B–induced oxidative stress in human lymphocytes[J]. Nutrition Research, 2007, 27: 559–564.
[5]. Nomura E., Hosoda A., Morishita H., et al. Synthesis of novel polyphenols consisted of ferulic and gallic acids,and their inhibitory effects on phorbol ester-induced Epstein–Barr virus activation and superoxide generation[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1069–1075.
[6]. Shinya S., Hiroshi O., Katsuhisa N., et al. Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, raw 264.7[J]. Cytokine, 1997, 9(4): 242-248.
[7].杨柳,吴本俨,顾瑛,等.阿魏酸钠治疗缺血性结肠炎的研究[J].中国新药杂志, 2007, 16(24): 2024-2026.
[8].胡益勇,徐晓玉.阿魏酸的化学和药理研究进展[J].中成药, 2006, 28(2): 253-254.
[9]. Surinder K.Y., Arunachalam G., Subramanian S., et al. Synergistic salubrious effect of ferulic acid and ascorbic acid on membrane-bound phosphatases and lysosomal hydrolases during experimental myocardial infaration in rats[J]. Life Sciences, 2006, 80: 258–263.
[10]. Nomura E., Kashiwada A., Hosoda A, et al. Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro[J]. Bioorganic and Medicinal Chemistry, 2003, 11: 3807–3813.
[11]. Atsuyo F., Hideyuki S., Asako D., et al. Ferulic acid prevents pathological and functionalabnormalities of the kidney in Otsuka Long-Evans Tokushima fatty diabetic rats[J]. Diabetes Research and Clinical Practice, 2008, 79: 11–17.
[12]. Wang T., Chen L.X., Long Y., et al. DNA damage induced by caffeic acid phenyl ester in the presence of Cu(II) ions:Potential mechanism of its anticancer properties[J]. Cancer Letter, 2008, doi: 10.1016/j. canlet. 2007. 12. 021.
[13]. Gururaj J., Marzia P., Rukhsana S., et al. In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE)from oxidative stress mediated by 2,2-azobis(2-amidino-propane) dihydrochloride (AAPH) or Fe2+/H2O2:Insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders[J]. Neurochemistry International, 2006, 48: 318-327.
[14]. Adluri R.S., Shanmugavel M., Nagarajan D., et al. Influence of ferulic acid on nicotine- induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine[J]. Toxicology, 2008, 243: 317-329.
[15]. Yang F., Zhou B.R., Zhang P., et al. Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis[J]. Chemico-Biological Interactions, 2007, 170: 231–243.
[16]. Yu L., Zhang Y., Ma R., et al. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain[J]. European Neuropsychopharmacology, 2006, 16: 170- 177.
[17]. Srinivasan M., Ram A.S., K.Raveendran P., et al. Influence of ferulic acid onγ-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes[J]. Toxicology, 2006, 228: 249–258.
[18].黄华永,沈海星,郑锦鸿.阿魏酸及其类似物的合成及其清除自由基活性研究[J].中国新药杂志, 2006, 15(6): 454-457.
[19]. Nomura E., Hosoda A., Morishita H., et al. Synthesis of novel polyphenols consisted of ferulic and gallic acids, and their inhibitory effects on phorbol ester-induced Epstein–Barr virus activation and superoxide generation[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1069–1075.
[20].刘鹰翔,计志忠,牟孝硕,等. (E)-4-芳酰氧基苯丙烯酸类衍生物的合成及抑癌活性[J].Journal of Chinese Pharmaceutical Sciences, 2002, 11(3): 73-77.
[21].刘鹰翔,计志忠,牟孝硕,等. (E)-4-酰氧基苯丙烯酸类衍生物的合成及抑癌活性[J].中国药物化学杂志, 2001, 11(2): 76-79.
[22].马玉卓,刘鹰翔.肉桂酰异阿魏酸的合成[J].广东药学, 2002, 12(4): 4-5.
[23]. Hosoda A., Ozaki Y., Kashiwada A., et al. Syntheses of ferulic acid derivatives and their suppressive effects on cyclooxygenase-2 promoter activity[J]. Bioorganic and Medicinal Chemistry, 2002, 10: 1189–1196.
[24]. Wang X., Salomon S., Phillip D., et al. Cytoprotective effect of caffeic acid phenethyl ester (CAPE) and catechol ring-fluorinated CAPE derivatives against menadione-induced oxidative stress in human endothelial cells[J]. Bioorganic and Medicinal Chemistry, 2006, 14: 4879–4887.
[25]. Moriyasu T., Tatsuji S., Tomoyuki F., et al. Esterification of ferulic acid with polyols using a ferulic acid esterase from Aspergillus niger[J]. Biochimica and Biophysica Acta, 2006, 1760: 1071–1079.
[26].刘鹰翔,汪金平,计志忠,等. 1-取代-2-(3-甲氧基-4-肉桂酰氧基)苯乙烯衍生物的合成及抗血小板聚集活性[J].中国药物化学杂志, 1996, 6(2): 79-84.
[27].刘鹰翔,马玉卓,江涛,等. (E)-4-芳酰氧基苯基丁烯-3-酮-2衍生物的合成及生物活性[J].中国药物化学杂志, 2000, 10(4): 242-245.
[28]. Nomura E., Kashiwada A., Hosoda A., et al. Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro[J]. Bioorganic and Medicinal Chemistry, 2003, 11: 3807–3813.
[29].刘鹰翔,马玉卓,计志忠,等. (E)-4-桂皮酰氧基苯乙烯衍生物的合成及抗炎活性[J].中国药物化学杂志, 1999, 9(3): 186-191.
[30]. Amselmi C., Centini M., Maggiore M., et al. Non-covalent inclusion of ferulic acid withα-cyclodextrin improves photo-stability and delivery:NMR and modeling studies[J]. Journal of Pharmaceutical and Biomedical Analysis, 2008, 46: 645–652.
[31]. Amselmi C., Centini M., Ricci M., et al. Analytical characterization of a ferulic acid/γ- cyclodextrin inclusion complex[J]. Journal of Pharmaceutical and Biomedical Analysis, 2006, 40: 875–881.
[32]. Rakotondramanana D.L.A., Melanie D., Michel B., et al. Synthesis of ferulic ester dimers,functionalisation and biological evaluation as potential antiatherogenic and antiplasmodial agents[J]. Bioorganic and Medicinal Chemistry, 2007, 15: 6018–6026.
[33]. Bernhard H.M., Brian L.H., Arjun R., et al. Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases[J]. Bioorganic and Medicinal Chemistry, 2006, 14: 7988–7998.
[34].闫雪梅,赵慧萍,严红.HPLC法测定通脉颗粒中阿魏酸的含量[J].中草药, 2003, 34(3): 230-231.
[35].宋金春,唐开勇.通脉口服液的质量标准研究[J].中国药房, 2006, 17(22): 1730-1732.
[36].运委,孙仲葆,刘戎.高效液相色谱法测定当归苦参丸中阿魏酸的含量[J].中国医院药学杂志, 2007, 27(10): 1477-1478.
[37].辛嘉英,郑妍,赵冠里,等.阿魏酸衍生物的应用及合成[J].化学世界, 2006, 5: 305- 306.
[38].吕以仙,陆阳,邓键等.有机化学.第6版[M].北京:人民卫生出版社,2004. 76-78.
[39].闻韧.药物合成反应.第2版[M].北京:化学工业出版社,2003. 213-216.
[40]. Hosoda A., Nomura E., Mizuno K., et al. Synthesis of feruloyl-myo-insitol derivatives and their inhibitory effects on phorbol ester-induced superoxide generation and esptein–barr virus activation[J]. Bioorganic and Medicinal Chemistry, 2002, 10(6): 1855–1863.
[41]. Hosoda A., Nomura E., Mizuno K., et al. Preparation of a(±)-1,6-Di-O-feruloyl-myo- inositol derivative: an efficient method for introduction of ferulic acid to 1,6-vicinal hydroxyl groups of myo-Inositol[J]. Journal of Organic Chemistry, 2001, 66: 7201.
[42].容国斌,朱士正.波谱数据表—有机化合物的结构解析.第2版[M].上海:华东理工大学出版社,2002. 164-367.
[43].宁永成.有机化合物结构鉴定与有机波谱学[M].北京:科学出版社,2000. 36-335.
[44].庞战军,周玟,陈瑗.自由基医学研究方法[M].北京:人民卫生出版社,2000. 14-15.
[45]. Zhao G., Xiang Z., Ye T., et al. Antioxidant activities of Salvia miltiorrhiza and Panax notoginseng[J]. Food Chemistry, 2006, 99: 767–774.
[46]. Lee C., Yoon J. Temperature dependence of hydroxyl radical formation in the hv/ Fe3+/H2O2 and Fe2+/H2O2 systems[J]. Chemosphere, 2004, 56: 923-934.
[47].李甘地,来茂德,杨光华等.病理学[M].北京:人民卫生出版社,2002. 81-82.
[48].李端,殷明,任雷鸣,等.药理学.第5版[M].北京:人民卫生出版社,2006. 166-173.
[49].赵一玫,夏丹,艾彩萍,等.布洛芬衍生物的合成及抗炎活性[J].中国药物化学杂志, 2005, 15(6): 360-362.
[50]. Zhang B., He X.L., Ding Y., et al. Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: Towards a better non-steroidal anti-inflammatory drug[J]. European Journal of Pharmacology, 2006, 530: 166-171.
[51].徐叔云,卞如濂,陈修等.药理实验方法学.第3版[M].北京:人民卫生出版社, 2002. 905-911.
[52]. Sander H., Anita H., Annemarie S., et al. Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice[J]. European Journal of Pharmacology, 2006, 531: 264–269.
[53]. Ramy R. H., Ashraf B.A., Amani E. K., et al. Anti-inflammatory effects of jojoba liquid wax in experimental models[J]. Pharmacological Research, 2005, 51: 95–105.
[54].邹移海,徐志伟,苏钢强等.实验动物学[M].北京:科学出版社,2004. 176-182.
[55].金丕焕,曹素华.医用统计方法[M].上海:复旦大学出版社,2002. 64-68.
[56]. Mavar-Manga H., Haddad M., Pieters L., et al. Anti-inflammatory compounds from leaves and root bark of Alchornea cordifolia (Schumach. and Thonn.) Mull. Arg.[J]. Journal of Ethnopharmacology, 2008, 115: 25–29.