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

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.

The synthesis and pharmacological evaluation of a series of novel amide and thioester conjugates between Danshensu and cysteine derivatives have been reported and 3a/4a/17a/6a–d demonstrated significant cardiovascular-protective effect.Figure optionsDownload as PowerPoint slideHighlights
► A series of conjugates between Danshensu and cysteine have been synthesized.
► The bioactivity assay showed significant protective effect on H2O2-induced HUVECs.
► The mechanism may be related to their anti-oxidative and anti-apoptotic properties.