Journal of Medicinal Chemistry p. 7501 - 7511 (2015)
Update date:2022-07-30
Topics:
Zhao, Yu
Yang, Chuntao
Organ, Chelsea
Li, Zhen
Bhushan, Shashi
Otsuka, Hiro
Pacheco, Armando
Kang, Jianming
Aguilar, Hector C.
Lefer, David J.
Xian, Ming
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.
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