title: Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors.
abstract: 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.
authors: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors: Yu
authors: Y
authors: Zhao
authors: Department of Physiology, Guangzhou Medical University , Guangzhou 511436, China.
authors: Chuntao
authors: C
authors: Yang
authors: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors: Chelsea
authors: C
authors: Organ
authors: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors: Zhen
authors: Z
authors: Li
authors: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors: Shashi
authors: S
authors: Bhushan
authors: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors: Hiro
authors: H
authors: Otsuka
authors: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors: Armando
authors: A
authors: Pacheco
authors: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors: Jianming
authors: J
authors: Kang
authors: Paul G. Allen School for Global Animal Health, Washington State University , Pullman, Washington 99164, United States.
authors: Hector C
authors: HC
authors: Aguilar
authors: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors: David J
authors: DJ
authors: Lefer
authors: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors: Ming
authors: M
authors: Xian
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D006352:Heart Ventricles / Q000166:cytology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008810:Mice, Inbred C57BL; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D018384:Oxidative Stress; D051381:Rats; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001549:Benzamides; D002316:Cardiotonic Agents; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D006862:Hydrogen Sulfide