Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland.
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Bioorg Chem. 2021 Mar;108:104650. doi: 10.1016/j.bioorg.2021.104650. Epub 2021 Jan 12.
Hydrogen sulfide (HS) is a gaseous molecule that exhibits various biological effects. For example, HS has been recognized as a blood pressure-lowering agent. Presented in this report is a new modifiable platform for HS supply, its preparation and HS release kinetics from a series of structurally diversified thionolactones. Furthermore, the properties of the obtained HS donors were evaluated in both in vitro and in vivo studies. The kinetic parameters of HS release were determined and compared with NaHS and pyrrolidine-2-thione, a thiolactame analog, using a fluorescence detection method based on 7-azido-4-methyl-2H-chromen-2-one probe. We have shown that HS release rates from the developed compounds are controllable through structural modifications. This study shows that both the thiono-lactone ring's size and the presence of a methyl group in the thiono-lactone ring significantly influenced the rate of HS release. Finally, we have found a significant hypotensive response to intravenous administration of the developed donors in anesthetized rats.
硫化氢(HS)是一种具有多种生物学效应的气态分子。例如,HS 已被认为是一种降低血压的物质。本报告介绍了一种新的可修饰的 HS 供应平台,以及一系列结构多样化的硫代内酰胺的 HS 释放动力学。此外,还在体外和体内研究中评估了所得 HS 供体的性质。通过基于 7-叠氮-4-甲基-2H-色烯-2-酮探针的荧光检测方法,确定了 HS 释放的动力学参数,并与 NaHS 和吡咯烷-2-硫酮(硫代内酰胺类似物)进行了比较。我们已经表明,通过结构修饰可以控制开发的化合物中 HS 的释放速率。这项研究表明,硫代内酰胺环的大小和硫代内酰胺环中甲基的存在都显著影响 HS 的释放速率。最后,我们发现静脉给予开发的供体在麻醉大鼠中产生了显著的降压反应。