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发现用于缓解缺氧性心脏病的高效缺氧靶向一氧化氮供体化合物。

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

作者信息

Yang Wanxiang, Zhou Wen, Gou Shaohua

机构信息

Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.

Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.

出版信息

J Med Chem. 2023 Dec 14;66(23):15977-15989. doi: 10.1021/acs.jmedchem.3c01421. Epub 2023 Nov 16.

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 was found to selectively release NO under hypoxia with a higher ratio than isosorbide dinitrate (ISDN). In vitro study indicated that 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 possessed a potent antimyocardial hypoxic injury effect superior to ISDN. These findings suggest that has a better effect on alleviating hypoxic cardiac disease than the conventional drug, owing to its hypoxia-targeted release of NO.

摘要

为了获得用于治疗缺氧性心脏病的高效一氧化氮供体药物,制备并筛选了一系列靶向缺氧的一氧化氮供体化合物。其中,发现一种代表性化合物在缺氧条件下能选择性释放一氧化氮,且释放比例高于硝酸异山梨酯(ISDN)。体外研究表明,即使在低浓度下,该化合物也能有效调节H9c2细胞中的血管舒张和心肌损伤相关蛋白,具有很强的缓解血管舒张和减轻心肌缺氧损伤的能力。通过腹腔注射或灌胃给药,体内动物试验表明,该化合物具有优于ISDN的强大抗心肌缺氧损伤作用。这些发现表明,由于其靶向缺氧释放一氧化氮,该化合物在缓解缺氧性心脏病方面比传统药物具有更好的效果。

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