Design, Synthesis, and Preliminary Cardioprotective Effect Evaluation of Danshensu Derivatives. (1st July 2014)

• Record Type: Journal Article
• Authors: Cui, Qingbin; Chen, Yonghong; Zhang, Mingjuan; Shan, Luchen; Sun, Yewei; Yu, Pei; Zhang, Gaoxiao; Wang, Dingyuan; Zhao, Zengchao; Xu, Qian; Xu, Benhong; Wang, Yuqiang
• Is Part Of: Chemical biology & drug design. Volume 84:Number 3(2014:Sep.)
• Page Start: 282
• Page End: 291
• Publication Date: 2014-07-01
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12312
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12312-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of (R)‐3, 4‐dihydroxyphenyllactic acid Danshensu (DSS) derivatives were synthesized, and their cardioprotective effects were evaluated <italic>in vitro</italic> and <italic>in vivo</italic>. Among the new derivatives, compound <bold>14</bold> showed significant protective effects in cultured myocardial cells and in the rat model of myocardial ischemia. The therapeutic efficacy of compound <bold>14</bold> was significantly higher than that of its parent compound DSS, and amlodipine, a first‐line treatment for angina pain. Compound <bold>14</bold> potently scavenged free radicals, significantly decreased the levels of LDH and MDA, and inhibited the leakage of CK in animal model of ischemia. We had previously found that compound <bold>14</bold> activated PI3K/Akt/GSK‐3<italic>β</italic> and Nrf2//Keap1/heme oxygenase‐1 (HO‐1) signaling pathways in H9c2 cells. These results suggest that compound <bold>14</bold> has a unique mechanism of action, that is, multifunctional. Compound <bold>14</bold> may be a new potential therapy for ischemic heart diseases.</p> </abstract>