Wang Wenyi, Wang Binghe
Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, United States.
Front Chem. 2018 Nov 16;6:559. doi: 10.3389/fchem.2018.00559. eCollection 2018.
SO is widely recognized as an air pollutant and is a known cause of acid rain. At a sufficiently high level, it also causes respiratory diseases. A much lesser known side of SO is its endogenous nature and possible physiological roles. There is mounting evidence that SO is produced during normal cellular metabolism and may possibly function as a signaling molecule in normal physiology. The latter aspect is still at the stage of being carefully examined as to the validity of classifying SO as a gasotransmitter with endogenous signaling roles. One difficulty in studying the biological and pharmacological roles of SO is the lack of adequate tools for its controllable and precise delivery. Traditional methods of using SO gas or mixed sulfite salts do not meet research need for several reasons. Therefore, there has been increasing attention on the need of developing SO donors or prodrugs that can be used as tools for the elucidation of SO's physiological roles, pharmacological effects, and possible mechanism(s) of action. In this review, we aim to review basic sulfur chemistry in the context of sulfur signaling and various chemical strategies used for designing SO donors. We will also discuss potential pharmacological applications of SO donors, lay out desirable features for such donors and possibly prodrugs, analyze existing problems, and give our thoughts on research needs.
二氧化硫被广泛认为是一种空气污染物，也是酸雨的已知成因。在足够高的浓度下，它还会引发呼吸道疾病。二氧化硫鲜为人知的另一面是其内源性质及可能的生理作用。越来越多的证据表明，二氧化硫在正常细胞代谢过程中产生，并且在正常生理状态下可能作为信号分子发挥作用。就将二氧化硫归类为具有内源性信号作用的气体递质这一分类的有效性而言，后一个方面仍处于仔细研究阶段。研究二氧化硫的生物学和药理学作用的一个困难在于缺乏用于可控且精确递送它的适当工具。使用二氧化硫气体或混合亚硫酸盐的传统方法由于多种原因无法满足研究需求。因此，开发可作为阐明二氧化硫生理作用、药理作用及可能作用机制的工具的二氧化硫供体或前药的需求受到越来越多的关注。在本综述中，我们旨在结合硫信号传导来综述基础硫化学以及用于设计二氧化硫供体的各种化学策略。我们还将讨论二氧化硫供体的潜在药理学应用，列出此类供体及可能的前药的理想特性，分析现存问题，并给出我们对研究需求的看法。
