Introduction

The gasotransmitter hydrogen sulphide (H₂S), an endogenous ubiquitous signalling molecule, is known for its beneficial effects on different mammalian systems. H₂S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury.

Methods

A library of forty-five isothiocyanates, selected for their different chemical properties, has been evaluated for its hydrogen sulfide (H₂S) releasing capacity. The obtained results allowed to correlate several factors such as steric hindrance, electronic effects and position of the substituents to the observed H₂S production. Moreover, the chemical-physical profiles of the selected compounds have been studied by an in silico approach and from a combination of the obtained results, 3-pyridyl-isothiocyanate (25) has been selected as the most promising one. A detailed pharmacological characterization of its cardioprotective action has been performed.

Results

The results herein obtained strongly indicate 3-pyridyl-isothiocyanate (25) as a suitable pharmacological option in anti-ischemic therapy. The cardioprotective effects of compound 25 were tested in vivo and found to exhibit a positive effect.

Conclusion

Results strongly suggest that isothiocyanate-based H₂S-releasing drugs, such as compound 25, can trigger a ‘‘pharmacological pre-conditioning” and could represent a suitable pharmacological option in antiischemic therapy.

中文翻译：

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异硫氰酸酯对 H2S 释放特性的构效关系研究：3-吡啶基异硫氰酸酯作为一种新的有前途的心脏保护剂

介绍

气体递质硫化氢 (H ₂ S) 是一种内源性无处不在的信号分子，以其对不同哺乳动物系统的有益影响而闻名。H ₂ S 表现出对缺血/再灌注 (I/R) 或缺氧损伤的心脏保护活性。

方法

已根据其不同的化学性质选择了 45 种异硫氰酸酯库，评估了其硫化氢 (H ₂ S) 释放能力。获得的结果允许将诸如空间位阻、电子效应和取代基的位置等几个因素与观察到的H ₂ S 产生相关联。此外，已通过计算机方法研究了所选化合物的化学-物理特性，并结合所获得的结果，选择了 3-吡啶基-异硫氰酸酯 (25) 作为最有希望的化合物。已经对其心脏保护作用进行了详细的药理学表征。

结果

本文获得的结果强烈表明 3-吡啶基-异硫氰酸酯 (25) 作为抗缺血治疗的合适药理学选择。在体内测试了化合物 25 的心脏保护作用，发现显示出积极作用。

结论

结果强烈表明，基于异硫氰酸酯的 H ₂ S 释放药物，例如化合物 25，可以触发“药理学预处理”，并且可以代表抗缺血治疗中的合适药理学选择。