Discovery of Efficient Hypoxia-Targeted NO Donor Compounds to Alleviate Hypoxia Cardiac Disease

  • J Med Chem. 2023 Nov 16. doi: 10.1021/acs.jmedchem.3c01421.
Wanxiang Yang  1 Wen Zhou  1  2 Shaohua Gou  1  2
Affiliations
  • 1. Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
  • 2. Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
Abstract

In order to obtain efficient NO donor drugs to treat hypoxic cardiac disease, a series of hypoxia-targeted NO donor compounds were prepared and screened. Among them, a representative compound H3 was found to selectively release NO under hypoxia with a higher ratio than isosorbide dinitrate (ISDN). In vitro study indicated that H3 had a strong capability of alleviating vascular dilation and reducing myocardial hypoxic injury due to its effective regulation of vascular dilatation and myocardial injury-related proteins in H9c2 cells even at low concentrations. By intraperitoneal injection or intragastric administration, in vivo animal tests revealed that H3 possessed a potent antimyocardial hypoxic injury effect superior to ISDN. These findings suggest that H3 has a better effect on alleviating hypoxic cardiac disease than the conventional drug, owing to its hypoxia-targeted release of NO.

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