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Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents.
Chem Commun (Camb) 2019; 55(44):6193-6196CC

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.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China. jinyixu@china.com cpuxst@cpu.edu.cn.No 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

Language

eng

PubMed ID

31070620

Citation

Yao, Hong, et al. "Controllable Thioester-based Hydrogen Sulfide Slow-releasing Donors as Cardioprotective Agents." Chemical Communications (Cambridge, England), vol. 55, no. 44, 2019, pp. 6193-6196.
Yao H, Luo S, Liu J, et al. Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents. Chem Commun (Camb). 2019;55(44):6193-6196.
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 (Cambridge, England), 55(44), pp. 6193-6196. doi:10.1039/c9cc02829c.
Yao H, et al. Controllable Thioester-based Hydrogen Sulfide Slow-releasing Donors as Cardioprotective Agents. Chem Commun (Camb). 2019 May 28;55(44):6193-6196. PubMed PMID: 31070620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents. AU - Yao,Hong, AU - Luo,Shanshan, AU - Liu,Junkai, AU - Xie,Shaowen, AU - Liu,Yanpeng, AU - Xu,Jinyi, AU - Zhu,Zheying, AU - Xu,Shengtao, PY - 2019/5/10/pubmed PY - 2019/6/25/medline PY - 2019/5/10/entrez SP - 6193 EP - 6196 JF - Chemical communications (Cambridge, England) JO - Chem. Commun. (Camb.) VL - 55 IS - 44 N2 - 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. SN - 1364-548X UR - https://www.unboundmedicine.com/medline/citation/31070620/Controllable_thioester_based_hydrogen_sulfide_slow_releasing_donors_as_cardioprotective_agents_ L2 - https://doi.org/10.1039/c9cc02829c DB - PRIME DP - Unbound Medicine ER -