期刊
CHEMICAL SCIENCE
卷 13, 期 12, 页码 3549-3555出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2sc00048b
关键词
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资金
- Natural Science Foundation of Jiangsu Province [BK20180570]
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research
In this study, a novel hypoxia-activated NO donor (Hano) was designed and prepared, which can increase NO release, dilate blood vessels, and attenuate myocardial hypoxia injury. This drug shows great potential for the treatment of hypoxic heart diseases.
As present NO donor drugs cannot localize to release NO at the hypoxic site, along with the short half-life and bidirectional regulation of NO, they are unable to overcome low bioavailability and side effects in the treatment of myocardial hypoxia injury. In this study, we designed and prepared a novel hypoxia-activated NO donor (Hano) by hybridization of a known NO donor compound (Nno) with a hypoxia-activated group. Hano and isosorbide dinitrate were compared in terms of NO release and anti-myocardial hypoxia injury. Furthermore, the effects of Hano and Nno on releasing NO, dilating blood vessels, and preventing myocardial hypoxia injury were studied and compared in smooth muscle cells, cardiomyocytes and mice. The results showed that the NO release by Hano increased either in smooth muscle cells or in myocardial cells under hypoxia conditions. Significantly, Hano was found capable of dilating blood vessels and attenuating hypoxia injury both in vitro and in vivo, and has great potential as a hypoxia-activated NO donor drug to treat hypoxic heart diseases.
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