Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents. Issue 44 (9th May 2019)

• Record Type: Journal Article
• Authors: Yao, Hong; Luo, Shanshan; Liu, Junkai; Xie, Shaowen; Liu, Yanpeng; Xu, Jinyi; Zhu, Zheying; Xu, Shengtao
• Is Part Of: Chemical communications. Volume 55:Issue 44(2019)
• Page Start: 6193
• Page End: 6196
• Publication Date: 2019-05-09
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c9cc02829c
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Hydrogen sulfide (H2 S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. Abstract : Hydrogen sulfide (H2 S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2 S has been impeded by the lack of appropriate H2 S donors that could mimic its slow-releasing process in vivo . Herein, we report the rational design, synthesis, and biological evaluation of a series of thioester-based H2 S donors. These cysteine-activated H2 S donors release H2 S in a slow and controllable manner. Most of the donors comprising an allyl moiety showed significant cytoprotective effects in H9c2 cellular models of oxidative damage. The most potent donor 5e decreased the mitochondrial membrane potential (MMP) loss and lactate dehydrogenase (LDH) release in H2 O2 -stimulated H9c2 cells. More importantly, donor 5e exhibited a potent cardioprotective effect in an in vivo myocardial infarction (MI) mouse model by reducing myocardial infarct size and cardiomyocyte apoptosis. Taken together, our studies demonstrated that these new allyl thioesters are potential cardioprotective agents by releasing H2 S.