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Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen Sulfide Donors.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2015 Sep 24; Vol. 58 (18), pp. 7501-11. Date of Electronic Publication: 2015 Sep 04. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Benzamides chemical synthesis
Benzamides chemistry
Benzamides pharmacology
Cardiotonic Agents chemical synthesis
Cardiotonic Agents pharmacology
Cell Line
Drug Design
Heart Ventricles cytology
Hydrogen Peroxide pharmacology
L-Lactate Dehydrogenase metabolism
Male
Membrane Potential, Mitochondrial drug effects
Mice, Inbred C57BL
Myoblasts, Cardiac cytology
Myoblasts, Cardiac drug effects
Myocardial Reperfusion Injury drug therapy
Oxidative Stress
Rats
Structure-Activity Relationship
Sulfhydryl Compounds chemical synthesis
Sulfhydryl Compounds pharmacology
Cardiotonic Agents chemistry
Hydrogen Sulfide metabolism
Sulfhydryl Compounds chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 58
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26317692
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.5b01033