Design,Synthesis, and Preliminary Cardioprotective Effect Evaluation of Danshensu Derivatives |
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| Authors: | Qingbin Cui Yonghong Chen Mingjuan Zhang Luchen Shan Yewei Sun Pei Yu Gaoxiao Zhang Dingyuan Wang Zengchao Zhao Qian Xu Benhong Xu Yuqiang Wang |
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| Affiliation: | Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, , Guangzhou, 510632 China |
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| Abstract: | A series of (R)‐3,4‐dihydroxyphenyllactic acid Danshensu (DSS) derivatives were synthesized, and their cardioprotective effects were evaluated in vitro and in vivo. Among the new derivatives, compound 14 showed significant protective effects in cultured myocardial cells and in the rat model of myocardial ischemia. The therapeutic efficacy of compound 14 was significantly higher than that of its parent compound DSS, and amlodipine, a first‐line treatment for angina pain. Compound 14 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 14 activated PI3K/Akt/GSK‐3β and Nrf2//Keap1/heme oxygenase‐1 (HO‐1) signaling pathways in H9c2 cells. These results suggest that compound 14 has a unique mechanism of action, that is, multifunctional. Compound 14 may be a new potential therapy for ischemic heart diseases. |
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| Keywords: | biological screening chemical synthesis Danshensu derivatives drug design myocardial ischemia |
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