title: pH-Controlled Hydrogen Sulfide Release for Myocardial Ischemia-Reperfusion Injury.
abstract: 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.
authors.affiliation: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors.forename: Jianming
authors.initials: J
authors.lastname: Kang
authors.affiliation: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Organ
authors.affiliation: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.|Department of Chemistry, Gangneung-Wonju National University , Gangneung, Gangwon 25457, South Korea.
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Park
authors.affiliation: Department of Physiology, Guangzhou Medical University , Guangzhou 511436, China.
authors.forename: Chun-Tao
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors.forename: Armando
authors.initials: A
authors.lastname: Pacheco
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center , Washington, D.C. 20057, United States.
authors.forename: Difei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Cardiovascular Center of Excellence, Louisiana State University Health Science Center , New Orleans, Louisiana 70112, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
authors.affiliation: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*
chemical_list: D006862:Hydrogen Sulfide