Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors

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• 作者：Yu Zhao ; Chuntao Yang ; Chelsea Organ ; Zhen Li ; Shashi Bhushan ; Hiro Otsuka ; Armando Pacheco ; Jianming Kang ; Hector C. Aguilar ; David J. Lefer ; Ming Xian
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：September 24, 2015
• 年：2015
• 卷：58
• 期：18
• 页码：7501-7511
• 全文大小：631K
• ISSN：1520-4804

文摘

Hydrogen sulfide (H₂S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H₂S levels could have great potential therapeutic value. In this work, we report the design, synthesis, and evaluation of a class of N-mercapto (N-SH)-based H₂S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H₂S release from these donors could be achieved upon structural modifications. Selected donors (NSHD-1, NSHD-2, and NSHD-6) were tested in cellular models of oxidative damage and showed significant cytoprotective effects. Moreover, NSHD-1 and NSHD-2 were also found to exhibit potent protective effects in a murine model of myocardial ischemia reperfusion (MI/R) injury.