Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents

Yao, Hong; Luo, Shanshan; Liu, Junkai; Xie, Shaowen; Liu, Yanpeng; Xu, Jinyi; Zhu, Zheying; Xu, Shengtao

Abstract

Hydrogen sulfide (H2S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2S has been impeded by the lack of appropriate H2S 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 H2S donors. These cysteine-activated H2S donors release H2S 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 H2O2-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 H2S.

Citation

Yao, H., Luo, S., Liu, J., Xie, S., Liu, Y., Xu, J., …Xu, S. (2019). Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents. Chemical Communications, 55(44), 6193-6196. https://doi.org/10.1039/c9cc02829c

• Journal Article Type: Article
• Acceptance Date: Apr 28, 2019
• Online Publication Date: Apr 30, 2019
• Publication Date: Jun 4, 2019
• Deposit Date: Jul 2, 2019
• Publicly Available Date: May 1, 2020
• Journal: Chemical Communications
• Print ISSN: 1359-7345
• Electronic ISSN: 1364-548X
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 55
• Issue: 44
• Pages: 6193-6196
• DOI: https://doi.org/10.1039/c9cc02829c
• Keywords: Materials chemistry; Electronic, Optical and magnetic materials; General chemistry; Surfaces, Coatings and films; Metals and alloys; Ceramics and composites; Catalysis
• Public URL: https://nottingham-repository.worktribe.com/output/2257555
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2019/CC/C9CC02829C#!divAbstract
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : Jinyi Xu (ORCID); : Authors can choose between single-blind and double-blind peer review; : Received 12 April 2019; Accepted 28 April 2019; Accepted Manuscript published 30 April 2019; Advance Article published 9 May 2019; Version of Record published 28 May 2019
• Contract Date: Jul 8, 2019