The physiological and pharmacological benefits of hydrogen sulfide (H₂S) are well established, and various H₂S and persulfide donors have been developed. However, few studies have examined the in vivo pharmacokinetics of sulfur donors, as most activity and metabolism tests are conducted in vitro, limiting insights into their clinical applications. This study utilized butylphthalide (NBP), an approved drug for ischemic stroke, by integrating H₂S and persulfide moieties directly into NBP’s carbonyl groups. We systematically compared drug metabolism in vitro and in vivo and evaluated donor efficacy in ischemia-reperfusion models. Results revealed notable in vitro/in vivo metabolic differences, with thioacid-containing donors showing promising therapeutic effects in cerebral ischemia, reducing infarct size, oxidative stress, and neuronal apoptosis.

中文翻译：

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缺血性卒中的双功能硫化物供体方法：利用丁苯酞作为硫化物前药的载体


硫化氢 （H₂S） 的生理和药理学益处已得到充分证实，并且已经开发了各种 H₂S 和过硫化物供体。然而，很少有研究检查硫供体的体内药代动力学，因为大多数活性和代谢测试都是在体外进行的，这限制了对其临床应用的了解。本研究利用丁苯酞 （NBP），一种获批用于治疗缺血性中风的药物，通过将 H₂S 和过硫化物部分直接整合到 NBP 的羰基中。我们系统地比较了体外和体内的药物代谢，并评估了缺血再灌注模型中的供体疗效。结果显示体外/体内代谢存在显着差异，含硫代酸的供体在脑缺血、减少梗死面积、氧化应激和神经元凋亡方面显示出有希望的治疗效果。