title: Synthesis and Biological Evaluation of Danshensu and Tetramethylpyrazine Conjugates as Cardioprotective Agents.
abstract: Myocardial ischemia is a primary cause of sudden death worldwide. Numerous active ingredients of traditional Chinese medicines including danshensu (DSS) and tetramethylpyrazine (TMP) have been widely used for the treatment of myocardial ischemia. To enhance their therapeutic efficacy and improve their drugability, in this work, we designed new DSS and TMP conjugates. Their water solubility and protective effects were studied in vitro and in experimental animal models. The new compounds demonstrated higher activities than the positive control agents acetylated danshensu and tetramethylpyrazine conjugate (ADTM) and salvianolic acid B (SAB) in preventing cells from oxidative insult. Among the new compounds, 14, bearing two glycine moieties, was more water soluble. In addition, compound 14 was much more potent in preventing cells from oxidative injury, at least 10- and 20-fold as potent as ADTM and SAB, respectively. The protective effects of compound 14 may be attributed to its anti-radical activity and anti-apoptotic activity. These results suggest that compound 14 is a promising candidate for the treatment of myocardial ischemia.
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy.
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.forename: Changjiang
authors.initials: C
authors.lastname: Xu
authors.forename: Gaoxiao
authors.initials: G
authors.lastname: Zhang
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Luchen
authors.initials: L
authors.lastname: Shan
authors.forename: Yewei
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007773:Lactates / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D002316:Cardiotonic Agents; D007773:Lactates; D011719:Pyrazines; C035055:3,4-dihydroxyphenyllactic acid; C017953:tetramethylpyrazine