title: The synthesis and biological evaluation of novel Danshensu-cysteine analog conjugates as cardiovascular-protective agents.
abstract: 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.
authors: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Yaoling
authors: Y
authors: Jia
authors: Xiaoyi
authors: X
authors: Dong
authors: Pengfei
authors: P
authors: Zhou
authors: Xinhua
authors: X
authors: Liu
authors: Lilong
authors: L
authors: Pan
authors: Hong
authors: H
authors: Xin
authors: Yi Zhun
authors: YZ
authors: Zhu
authors: Yang
authors: Y
authors: Wang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003545:Cysteine / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D002316:Cardiotonic Agents; D007773:Lactates; C035055:3,4-dihydroxyphenyllactic acid; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine