Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors

[Image: see text] Hydrogen sulfide (H(2)S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H(2)S levels could have great potential therapeutic value. In this work, we report the design, synthesis, and evaluation of a...

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Autores principales: Zhao, Yu, Yang, Chuntao, Organ, Chelsea, Li, Zhen, Bhushan, Shashi, Otsuka, Hiro, Pacheco, Armando, Kang, Jianming, Aguilar, Hector C., Lefer, David J., Xian, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766970/
https://www.ncbi.nlm.nih.gov/pubmed/26317692
http://dx.doi.org/10.1021/acs.jmedchem.5b01033
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author Zhao, Yu
Yang, Chuntao
Organ, Chelsea
Li, Zhen
Bhushan, Shashi
Otsuka, Hiro
Pacheco, Armando
Kang, Jianming
Aguilar, Hector C.
Lefer, David J.
Xian, Ming
author_facet Zhao, Yu
Yang, Chuntao
Organ, Chelsea
Li, Zhen
Bhushan, Shashi
Otsuka, Hiro
Pacheco, Armando
Kang, Jianming
Aguilar, Hector C.
Lefer, David J.
Xian, Ming
author_sort Zhao, Yu
collection PubMed
description [Image: see text] Hydrogen sulfide (H(2)S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H(2)S 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 H(2)S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H(2)S 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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spelling pubmed-47669702016-08-28 Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors Zhao, Yu Yang, Chuntao Organ, Chelsea Li, Zhen Bhushan, Shashi Otsuka, Hiro Pacheco, Armando Kang, Jianming Aguilar, Hector C. Lefer, David J. Xian, Ming J Med Chem [Image: see text] Hydrogen sulfide (H(2)S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H(2)S 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 H(2)S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H(2)S 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. American Chemical Society 2015-08-28 2015-09-24 /pmc/articles/PMC4766970/ /pubmed/26317692 http://dx.doi.org/10.1021/acs.jmedchem.5b01033 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Zhao, Yu
Yang, Chuntao
Organ, Chelsea
Li, Zhen
Bhushan, Shashi
Otsuka, Hiro
Pacheco, Armando
Kang, Jianming
Aguilar, Hector C.
Lefer, David J.
Xian, Ming
Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title_full Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title_fullStr Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title_full_unstemmed Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title_short Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors
title_sort design, synthesis, and cardioprotective effects of n-mercapto-based hydrogen sulfide donors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766970/
https://www.ncbi.nlm.nih.gov/pubmed/26317692
http://dx.doi.org/10.1021/acs.jmedchem.5b01033
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