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

[Image: see text] Hydrogen sulfide (H(2)S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H(2)S 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 H(2)S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H(2)S 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.