Yang Wanxiang, Zhou Wen, Gou Shaohua
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.
J Med Chem. 2023 Dec 14;66(23):15977-15989. doi: 10.1021/acs.jmedchem.3c01421. Epub 2023 Nov 16.
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.
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。