European Journal of Medicinal Chemistry 2012-09-01

The synthesis and biological evaluation of novel Danshensu-cysteine analog conjugates as cardiovascular-protective agents.

Yaoling Jia, Xiaoyi Dong, Pengfei Zhou, Xinhua Liu, Lilong Pan, Hong Xin, Yi Zhun Zhu, Yang Wang

文献索引：Eur. J. Med. Chem. 55 , 176-87, (2012)

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摘要

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 H(2)O(2)-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.Copyright © 2012 Elsevier Masson SAS. All rights reserved.