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

Authors
Journal
European Journal of Medicinal Chemistry
0223-5234
Publisher
Elsevier
Volume
55
Identifiers
DOI: 10.1016/j.ejmech.2012.07.016
Keywords
  • Danshensu
  • Cysteine
  • Conjugate
  • Cardiovascular-Protective
Disciplines
  • Biology
  • Chemistry
  • Design
  • Medicine

Abstract

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 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.

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