title: Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury.
abstract: Hydrogen sulfide (H2S), known as an important cellular signaling molecule, plays critical roles in many physiological and/or pathological processes. Modulation of H2S levels could have tremendous therapeutic value. However, the study on H2S has been hindered due to the lack of controllable H2S releasing agents that could mimic the slow and moderate H2S release in vivo. In this work we report the design, synthesis, and biological evaluation of a new class of controllable H2S donors. Twenty-five donors were prepared and tested. Their structures were based on a perthiol template, which was suggested to be involved in H2S biosynthesis. H2S release mechanism from these donors was studied and proved to be thiol-dependent. We also developed a series of cell-based assays to access their H2S-related activities. H9c2 cardiac myocytes were used in these experiments. We tested lead donors' cytotoxicity and confirmed their H2S production in cells. Finally we demonstrated that selected donors showed potent protective effects in an in vivo murine model of myocardial ischemia-reperfusion injury, through a H2S-related mechanism.
authors.affiliation: Department of Chemistry and ∥Paul G. Allen School for Global Animal Health, Washington State University , Pullman, Washington 99164, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.forename: Chuntao
authors.initials: C
authors.lastname: Yang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Otsuka
authors.forename: Jason D
authors.initials: JD
authors.lastname: Stein
authors.forename: Armando
authors.initials: A
authors.lastname: Pacheco
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Nelmi O
authors.initials: NO
authors.lastname: Devarie-Baez
authors.forename: Hector C
authors.initials: HC
authors.lastname: Aguilar
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
mesh_terms: D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D013438:Sulfhydryl Compounds; D006862:Hydrogen Sulfide
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