pH-Controlled Hydrogen Sulfide Release for Myocardial Ischemia-Reperfusion Injury

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• 作者：Jianming Kang ; Zhen Li ; Chelsea L. Organ ; Chung-Min Park ; Chun-tao Yang ; Armando Pacheco ; Difei Wang ; David J. Lefer ; Ming Xian
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：May 25, 2016
• 年：2016
• 卷：138
• 期：20
• 页码：6336-6339
• 全文大小：345K
• 年卷期：0
• ISSN：1520-5126

文摘

Hydrogen sulfide (H₂S) is a critical signaling molecule that regulates many physiological and/or pathological processes. Modulation of H₂S levels could have potential therapeutic value. In this work, we report the rational design, synthesis, and biological evaluation of a class of phosphonamidothioate-based H₂S-releasing agents (i.e., H₂S donors). A novel pH-dependent intramolecular cyclization was employed to promote H₂S release from the donors. These water-soluble compounds showed slow, controllable, and pH-sensitive production of H₂S in aqueous solutions. The donors also showed significant cytoprotective effects in cellular models of oxidative damage. Most importantly, the donors were found to exhibit potent cardioprotective effects in an in vivo murine model of myocardial ischemia-reperfusion (MI/R) injury through a H₂S-related mechanism.