新型丹参素衍生物的合成与抗心肌缺血活性研究

田霖; 郭海霞; 张洁; 焦育强; 吴秋业; 张川

doi:10.3969/j.issn.1006-0111.2015.06.012

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新型丹参素衍生物的合成与抗心肌缺血活性研究

田霖, 郭海霞, 张洁, 焦育强, 吴秋业, 张川

文章导航 > 药学实践与服务 > 2015 > 33(6): 525-528,535

田霖, 郭海霞, 张洁, 焦育强, 吴秋业, 张川. 新型丹参素衍生物的合成与抗心肌缺血活性研究[J]. 药学实践与服务, 2015, 33(6): 525-528,535. doi: 10.3969/j.issn.1006-0111.2015.06.012

引用本文:

TIAN Lin, GUO Haixia, ZHANG Jie, JIAO Yuqiang, WU Qiuye, ZHANG Chuan. Synthesis and anti-myocardial ischemia activities of novel Danshensu derivatives[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(6): 525-528,535. doi: 10.3969/j.issn.1006-0111.2015.06.012

Citation:

TIAN Lin, GUO Haixia, ZHANG Jie, JIAO Yuqiang, WU Qiuye, ZHANG Chuan. Synthesis and anti-myocardial ischemia activities of novel Danshensu derivatives[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(6): 525-528,535. doi: 10.3969/j.issn.1006-0111.2015.06.012

新型丹参素衍生物的合成与抗心肌缺血活性研究

doi: 10.3969/j.issn.1006-0111.2015.06.012

田霖¹,
郭海霞²,
张洁³,
焦育强⁴,
吴秋业⁵,
张川^1,

1.
福建中医药大学药学院, 福建福州 350122;第二军医大学药学院中药鉴定教研室上海 200433
2.
解放军266医院医务处, 河北承德 067000
3.
国防大学第二门诊部, 北京 100039
4.
福建中医药大学药学院, 福建福州 350122;第二军医大学药学院上海 200433
5.
第二军医大学药学院有机化学教研室, 上海 200433

Synthesis and anti-myocardial ischemia activities of novel Danshensu derivatives

1.
niversity of Traditional Chinese Medicine, Fuzhou 350122, China;Department of Science for Identifying Chinese Materia Medica, Second Military Medical University, Shanghai 200433, China
2.
No.266 Hospital of PLA, Chengde 067000, China
3.
Second Out-patient Department, National Defence University, Beijing 100039, China
4.
niversity of Traditional Chinese Medicine, Fuzhou 350122, China;Second Military Medical University, Shanghai 200433, China
5.
Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

摘要: 目的通过对丹参素进行结构改造,以改善其稳定性和药理活性。方法以中药提取的丹参素钠为起始化合物,经酯化反应、甲氧基保护酚羟基、硝化反应等合成新型的丹参素衍生物。建立心肌细胞缺氧模型,用MTT方法检测丹参素及其衍生物对缺氧H9c2细胞的保护作用。结果合成了15个全新的丹参素衍生物,并对其进行结构验证;药理活性实验显示,只有少数目标化合物在浓度为5 μmol/L时表现出强于丹参素的活性。结论多数化合物的最大药理活性未显现在所选浓度范围内,其活性未必低于丹参素,尚需做进一步探讨。
- 丹参素 /
- 结构修饰 /
- 合成 /
- 药理活性
Abstract: Objective To design and synthesize novel Danshensu derivatives in order to improve their stability and cardio-protective effect against myocardial ischemia. Methods Novel Danshensu derivatives were synthesized chiefly via esterification,methoxy phenol hydroxyl protection,nitration and amine solution reaction. All the target compounds were evaluated their biological effects on anti-myocardial ischemia with H9c2 cells in vitro. Results 15 compounds were synthesized and further confirmed by ¹H NMR and MS. Pharmacological studies showed that few synthetic derivatives at 5 μmol/L performed a higher biological effect than Danshensu. Conclusion Most derivatives didn't show the best activity at the chosen concentration gradient that a further pharmacological trial need to be done.
- Danshensu /
- structure modification /
- synthesis /
- pharmacological activity

[1]	李承珠,嘉宝,杨诗春,等.丹参素对血小板释放血管收缩物质的影响[J].中西医结合杂志,1984,4(9):532-565.
[2]	顾扬洪,张彩英,黄桂秋,等.丹参和丹参素对牛内皮细胞抗凝和纤溶功能的影响[J].第二军医大学学报,1990,10(3):208-212.
[3]	孙锡铭,蔡海江,宋素云,等.丹参素的新药理作用[J].中草药,1991,21(1):20-23.
[4]	王南,蔡海江,朱宇,等.丹参素对牛主动脉平滑肌细胞氧化修饰LDL的抑制作用[J].南京医科大学学报,1994,14(4):529-531.
[5]	蒋莉,李跃华,戚晓红,等.丹参素对内毒素性肝损伤的防护作用及其机制[J].中西医结合肝病杂志,1999,9(2):30-32.
[6]	郑元义,戴立里,王文兵,等.丹参素治疗肝纤维化及其作用机制研究[J].中华肝脏病杂志,2003,11(5):288-290.
[7]	王文俊,吴咸中,姚智,等.大黄索、丹参素对单核细胞分泌炎性细胞因子的调节[J].中国免疫学杂志,1995,11(6):370-372.
[8]	Lam FFY,Yeung JHK,Chan KM,et al.Relaxant effects of danshen aqueous extract and its constituent Danshensu on rat coronary artery are mediated by inhibition of calcium channels[J].Vascul Pharmacol,2007,46(4):271-277.
[9]	Zhao GR,Zhang HM,Ye TX,et al.Characterization of the radical scavenging and antioxidant activities of Danshensu and salvianolic acid B[J].Food ChemToxicol,2008,46(1):73-81.
[10]	眭建,林枫.丹参素对胃腺癌 NGCC细胞株的作用[J].镇江医学院学报,1997,7(4):384-285.
[11]	方杰. 丹参素对乳腺癌MCF细胞株的作用[J].中国老年学杂志,2003,3(23):168-169.
[12]	方芳,王平珍,邱芸.中药丹参的临床研究进展[J].内蒙古中医药,2012,19:81-82.
[13]	权伟,周丹,郭超,等.丹参素钠通过抑制炎症反应对心肌缺血-再灌注损伤的保护作用[J].中南药学,2012,10(12):885-888.
[14]	程彰华,楼亚平,戴华娟,等.丹参素对微循环障碍和血浆乳酸含量影响的实验研究[J].上海医科大学学报,1987,14(1):25-29.
[15]	王定远. 新型丹参素衍生物的合成及初步活性研究[D].广州:广州大学,2011.
[16]	Dong CN,WangY,Zhu YZ.Asymmetric synthesis and biological evaluation of Danshensu derivatives as anti-myocardial ischemia drug candidates[J].Bioorg Med Chem,2009,17:3499-3507.
[17]	张智波,董纪昌,金昔陆,等.八种丹参素衍生物的合成[J].上海医科大学学报,1996,23(增刊):26-28.
[18]	崔庆彬,单璐琛,朱华,等.丹参素结构中醇羟基的修饰与初步活性评价[J].国际药学研究杂志,2013,40(6):795-800.
[19]	郑晓辉,张群正,王世祥,等.β-(3,4-二羟基苯基)-α-羟基丙酸异丙酯、其合成方法和用途:中国,CN200610042787.3[P].2006-05-15.
[20]	向卓,景临林,刘文中,等.乙酰丹参素单硝酸异山梨醇酯的合成及对心肌缺血/再灌注大鼠心肌的保护作用[J].第四军医大学学报,2009,30(14):1257-1261.
[21]	Wang TF,Shu JJ.Synthesis and biological activities of novel Danshensu amide derivatives as anti-myocardial ischemia agents[J].Lat Am J Pharm,2011,30(7),1355-1359.
[22]	朱依谆,王洋,董村南,等.一种丹参素衍生物及其制备方法和在药学上的应用:中国,CN200810039162.0[P].2008-06-18.

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新型丹参素衍生物的合成与抗心肌缺血活性研究

doi: 10.3969/j.issn.1006-0111.2015.06.012

1. 福建中医药大学药学院, 福建福州 350122;第二军医大学药学院中药鉴定教研室上海 200433

2. 解放军266医院医务处, 河北承德 067000

3. 国防大学第二门诊部, 北京 100039

4. 福建中医药大学药学院, 福建福州 350122;第二军医大学药学院上海 200433

5. 第二军医大学药学院有机化学教研室, 上海 200433

收稿日期: 2015-01-23
修回日期: 2015-04-02

关键词:

丹参素 /

结构修饰 /

合成 /

药理活性

摘要: 目的通过对丹参素进行结构改造,以改善其稳定性和药理活性。方法以中药提取的丹参素钠为起始化合物,经酯化反应、甲氧基保护酚羟基、硝化反应等合成新型的丹参素衍生物。建立心肌细胞缺氧模型,用MTT方法检测丹参素及其衍生物对缺氧H9c2细胞的保护作用。结果合成了15个全新的丹参素衍生物,并对其进行结构验证;药理活性实验显示,只有少数目标化合物在浓度为5 μmol/L时表现出强于丹参素的活性。结论多数化合物的最大药理活性未显现在所选浓度范围内,其活性未必低于丹参素,尚需做进一步探讨。

English Abstract

Synthesis and anti-myocardial ischemia activities of novel Danshensu derivatives

1. niversity of Traditional Chinese Medicine, Fuzhou 350122, China;Department of Science for Identifying Chinese Materia Medica, Second Military Medical University, Shanghai 200433, China

2. No.266 Hospital of PLA, Chengde 067000, China

3. Second Out-patient Department, National Defence University, Beijing 100039, China

4. niversity of Traditional Chinese Medicine, Fuzhou 350122, China;Second Military Medical University, Shanghai 200433, China

5. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-01-23
Rev Recd Date: 2015-04-02

Keywords:

Abstract: Objective To design and synthesize novel Danshensu derivatives in order to improve their stability and cardio-protective effect against myocardial ischemia. Methods Novel Danshensu derivatives were synthesized chiefly via esterification,methoxy phenol hydroxyl protection,nitration and amine solution reaction. All the target compounds were evaluated their biological effects on anti-myocardial ischemia with H9c2 cells in vitro. Results 15 compounds were synthesized and further confirmed by ¹H NMR and MS. Pharmacological studies showed that few synthetic derivatives at 5 μmol/L performed a higher biological effect than Danshensu. Conclusion Most derivatives didn't show the best activity at the chosen concentration gradient that a further pharmacological trial need to be done.