Sulfur dioxide (SO2) has been recognized as a potential signaling molecule in cardiovascular systems. Although SO2's exact mechanisms of action are still under investigation, the production of endogenous SO2 and the exogenous administration of SO2 have been demonstrated to exert protective effects in models of certain cardiovascular diseases. These results strongly suggest that modulation of SO2 levels could have potential therapeutic values. In this field, suitable SO2 releasing agents (i.e. donors) are important research tools for better understanding the roles of SO2 in cardiovascular systems. The donors are also potential therapeutic agents. Unfortunately, only very few SO2 donors are currently known. Moreover, these compounds are not ideal for biological studies due to their bio-incompatible SO2 release mechanisms. This represents a significant limitation for fundamental SO2 studies, as well as for the use of SO2 therapy in chronic cardiovascular and other disease states. Our recent study revealed that benzothiazole sulfinate (BTS) is a suitable template for the design of novel SO2 donors. In this project, our goal is to develop and optimize long-lasting and controllable SO2 donor based on BTS and related structures. We will also explore cardioprotective actions of the donors in cell models of myocardial ischemia/reperfusion (MI/R) injury. We expect promising candidates will be identified for future evaluations in animal models of MI/R and heart failure.
The fields of sulfur dioxide (SO2) physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of SO2 in the future. In this project, we plan to develop a toolbox of long-lasting and controllable SO2 releasing agents and apply them to explore the pharmacology of SO2 under pathological disease states in in vitro model systems. We expect these studies will have great impact on SO2- related biomedical research.
| Day, Jacob J; Neill, Deshka L; Xu, Shi et al. (2017) Benzothiazole Sulfinate: A Sulfinic Acid Transfer Reagent under Oxidation-Free Conditions. Org Lett 19:3819-3822 |
| Chen, Wei; Xu, Shi; Day, Jacob J et al. (2017) A General Strategy for Development of Near-Infrared Fluorescent Probes for Bioimaging. Angew Chem Int Ed Engl 56:16611-16615 |
