The synthesis and biological evaluation of novel Danshensu-cysteine analog conjugates as cardiovascular-protective agents
The synthesis and biological evaluation of novel Danshensu-cysteine analog conjugates as cardiovascular-protective agents
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新型丹参素-半胱氨酸类似物缀合物心血管保护剂的合成及生物学评价
DOI：
10.1016/j.ejmech.2012.07.016
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发表时间：
2012-09-01
影响因子：
6.7
通讯作者：
Wang, Yang
中科院分区：
文献类型：
--
作者：
Jia, Yaoling;Dong, Xiaoyi;Wang, Yang
基于“药物化学杂交”的策略，设计并合成了一系列新型丹参素与半胱氨酸衍生物的酰胺和硫酯共轭物。药理学研究表明，酰胺偶联物3a/4a/17 a和硫酯偶联物6a-d对H2 O2诱导的人脐静脉内皮细胞（HUVECs）有明显的保护作用。这些偶联物预处理可提高谷胱甘肽（GSH）活性，降低丙二醛（MDA）水平。对化合物4a作用机制的进一步研究表明，其作用机制与其对肿瘤细胞的保护作用及对凋亡相关蛋白Bax、p53、PARP、caspase-3、caspase-9和Bcl-2表达的调节有关。这些结果表明，这些丹参素-半胱氨酸类似物共轭物具有显着的心血管保护作用，值得进一步研究。(C)2012年Elsevier Masson SAS。All rights reserved.
A series of novel amide and thioester conjugates between Danshensu and cysteine derivatives have been designed and synthesized based on the strategy of "medicinal chemical hybridization". Pharmacological evaluation indicated that the amide conjugates 3a/4a/17a and thioester conjugates 6a-d exhibited obvious protective effects on H2O2-induced human umbilical vein endothelial cells (HUVECs). Pretreated with these conjugates could increase glutathione (GSH) activity and decrease malondialdehyde (MDA) level. Further study on mechanism of compound 4a revealed that it was related to its mitochondrial-protective effect and regulation of apoptosis-related proteins expression (Bax, p53, PARP, caspase-3, caspase-9 and Bcl-2). These results indicate that these Danshensu-cysteine analog conjugates possess significant cardiovascular-protective effects and merit further investigation. (C) 2012 Elsevier Masson SAS. All rights reserved.