• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

川芎嗪/查耳酮类杂合物的设计、合成及抗血小板聚集活性

高洋, 尹伟, 刘靖超, 康峰华, 简琰琳, 周金培, 黄张建, 张奕华

高洋, 尹伟, 刘靖超, 康峰华, 简琰琳, 周金培, 黄张建, 张奕华. 川芎嗪/查耳酮类杂合物的设计、合成及抗血小板聚集活性[J]. 中国药科大学学报, 2017, 48(1): 23-30. DOI: 10.11665/j.issn.1000-5048.20170104
引用本文: 高洋, 尹伟, 刘靖超, 康峰华, 简琰琳, 周金培, 黄张建, 张奕华. 川芎嗪/查耳酮类杂合物的设计、合成及抗血小板聚集活性[J]. 中国药科大学学报, 2017, 48(1): 23-30. DOI: 10.11665/j.issn.1000-5048.20170104
shu
GAO Yang, YIN Wei, LIU Jingchao, KANG Fenghua, JIAN Yanlin, ZHOU Jinpei, HUANG Zhangjian, ZHANG Yihua. Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids[J]. Journal of China Pharmaceutical University, 2017, 48(1): 23-30. DOI: 10.11665/j.issn.1000-5048.20170104
Citation: GAO Yang, YIN Wei, LIU Jingchao, KANG Fenghua, JIAN Yanlin, ZHOU Jinpei, HUANG Zhangjian, ZHANG Yihua. Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids[J]. Journal of China Pharmaceutical University, 2017, 48(1): 23-30. DOI: 10.11665/j.issn.1000-5048.20170104
shu

川芎嗪/查耳酮类杂合物的设计、合成及抗血小板聚集活性

  • 中国药科大学新药研究中心

Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids

摘要

    摘要
  • 摘要: 基于药物设计的生物电子等排和拼合原理，设计、合成了一系列川芎嗪/查耳酮类杂合物( 2 ~ 26 )，以期得到活性较强的抗血小板聚集药物。结果表明，目标化合物对二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集均显示不同程度的抑制，其中化合物 8 活性最强，对ADP诱导的血小板聚集的抑制作用(IC50=0.14 mmol/L)是川芎嗪的9.1倍，查耳酮的10.5倍；对AA诱导的血小板聚集的抑制作用(IC50=0.09 mmol/L)是川芎嗪的8.8倍，查耳酮的10.0倍，且略优于阿司匹林(IC50=0.15 mmol/L)。
    Abstract: In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine(TMP)/chalcone hybrids( 2 - 26 )were synthesized and evaluated based on the principle of bioisostere and hybridization. They exerted inhibitory activity against adenosine diphosphate(ADP)-induced and arachidonic acid(AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation(9. 1 folds of TMP and 10. 5 folds of chalcone)and 0. 09 mmol/L on AA-induced platelet aggregation(8. 8 folds of TMP and 10. 0 folds of chalcone), which was superior to clinically used anti-platelet drug aspirin(ASP, IC50=0. 15 mmol/L).
    • HTML全文
    • 参考文献(12)
  • [1] Ohira T,Shahar E,Chambless LE,et al.Risk factors for ischemic stroke subtypes the atherosclerosis risk in communities study[J].Stroke,2006,37(10):2493-2498.
    [2] Uchiyama S,Demaerschalk BM,Goto S,et al.Stroke prevention by cilostazol in patients with atherothrombosis:meta-analysis of placebo-controlled randomized trials[J].J Stroke Cerebrovasc Dis,2009,18(6):482-490.
    [3] Yang CY,Huang ZJ,Ling JJ,et al.Synthesis and evaluation of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids as novel platelet aggregation inhibitors[J].J China Pharm Univ(中国药科大学学报),2013,44(3):202-206.
    [4] Ren Y,Liu EH,Lan L,et al. Protective effects and possible mechanism of Xingxiong sodium chloride injection on cerebral ischemia-reperfusion injury in rats[J].J China Pharm Univ (中国药科大学学报),2015,46(6):719-723.
    [5] Deng L, Guo X, Zhai L, et al. Ligustrazine derivatives. part 4:design,synthesis,and biological evaluation of novel ligustrazine-based stilbene derivatives as potential cardiovascular agents[J].Chem Biol Drug Des,2012,79(5):731-739.
    [6] Li G, Xu X, Xu K, et al. Ligustrazinyl amides: a novel class of ligustrazine-phenolic acid derivatives with neuroprotective effects[J].Chem Cent J,2015,9(1):1-9.
    [7] Benzhong M.Analysis of clinical efficacy of ligustrazine and xuesaitong on the treatment of ischemic stroke[J].Med Innov Chin(中国医学创新),2013,10(9):32-33.
    [8] Hu WY,Chen J,Jiang ZY,et al.Synthesis and biological activity of chalcone derivatives as potent activators of Nrf2[J].J China Pharm Univ (中国药科大学学报),2016,47(6):666-672.
    [9] Wu CM,Lin KW,Teng CH,et al.Chalcone derivatives inhibit human platelet aggregation and inhibit growth in human bladder cancer cells[J].Biol Pharm Bull,2014,37(7):1191-1198.
    [10] Sahu NK,Balbhadra SS,Choudhary J,et al.Exploring pharmacological significance of chalcone scaffold:a review[J].Curr Med Chem,2012,19(2):209-225.
    [11] Schumann H,Luo HK.2,5-Dimethyl-3,6-bis[(2,6-diisopropylphenylimino)methyl]-and 2,6-Bis[(2,6-diisopropylphenylimino)methyl]pyrazine:two new chelating ligands for transition metal complexes[J].Z Naturforsch B,2014,60(1):22-24.
    [12] Born GVR,Cross MJ.The aggregation of blood platelets[J].J Physiol,1963,168(1):178-195.
    • 相关文章
    • 施引文献
    • 资源附件(0)
计量
  • 文章访问数:  1216
  • HTML全文浏览量:  0
  • PDF下载量:  1680
  • 被引次数: 0
出版历程
  • 刊出日期:  2017-02-24

目录

摘要
HTML全文
    参考文献(12)
    相关文章
    施引文献
    资源附件(0)

    /

    返回文章
    返回

    版权所有：《中国药科大学学报》编辑部苏ICP备05007142号

    地址：江苏省南京市鼓楼区童家巷24号（210009）电话: 025-83271566E-mail: xuebao@cpu.edu.cn

    本系统由 北京仁和汇智信息技术有限公司 开发  百度统计

    访问量：414080