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Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury.
ACS Chem Biol 2013; 8(6):1283-90AC

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+Show Affiliations

Department of Chemistry and ∥Paul G. Allen School for Global Animal Health, Washington State University , Pullman, Washington 99164, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23547844

Citation

Zhao, Yu, et al. "Controllable Hydrogen Sulfide Donors and Their Activity Against Myocardial Ischemia-reperfusion Injury." ACS Chemical Biology, vol. 8, no. 6, 2013, pp. 1283-90.
Zhao Y, Bhushan S, Yang C, et al. Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury. ACS Chem Biol. 2013;8(6):1283-90.
Zhao, Y., Bhushan, S., Yang, C., Otsuka, H., Stein, J. D., Pacheco, A., ... Xian, M. (2013). Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury. ACS Chemical Biology, 8(6), pp. 1283-90. doi:10.1021/cb400090d.
Zhao Y, et al. Controllable Hydrogen Sulfide Donors and Their Activity Against Myocardial Ischemia-reperfusion Injury. ACS Chem Biol. 2013;8(6):1283-90. PubMed PMID: 23547844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury. AU - Zhao,Yu, AU - Bhushan,Shashi, AU - Yang,Chuntao, AU - Otsuka,Hiroyuki, AU - Stein,Jason D, AU - Pacheco,Armando, AU - Peng,Bo, AU - Devarie-Baez,Nelmi O, AU - Aguilar,Hector C, AU - Lefer,David J, AU - Xian,Ming, Y1 - 2013/04/16/ PY - 2013/4/4/entrez PY - 2013/4/4/pubmed PY - 2014/8/29/medline SP - 1283 EP - 90 JF - ACS chemical biology JO - ACS Chem. Biol. VL - 8 IS - 6 N2 - 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. SN - 1554-8937 UR - https://www.unboundmedicine.com/medline/citation/23547844/Controllable_hydrogen_sulfide_donors_and_their_activity_against_myocardial_ischemia_reperfusion_injury_ L2 - https://dx.doi.org/10.1021/cb400090d DB - PRIME DP - Unbound Medicine ER -