Prodrugs of Persulfides, Sulfur Dioxide, and Carbon Disulfide: Important Tools for Studying Sulfur Signaling at Various Oxidation States
Bingchen Yu, Zhengnan Yuan, Xiaoxiao Yang, Binghe Wang
Abstract
Significance: Bioactive sulfur species such as hydrogen sulfide (H 2 S), persulfide species (R-S n SH, n ≥ 1), hydrogen polysulfide (H 2 S n , n ≥ 2), sulfur dioxide (SO 2 ), and carbon disulfide (CS 2 ) participate in various physiological and/or pathological pathways such as vasodilation, apoptosis, inflammation, and energy metabolism regulation. The oxidation state of the individual sulfur species endows them unique biological activities. Recent Advances: There have been great strides made in achieving molecular understanding of the sulfur-signaling processes. Critical Issues: The development of various chemical tools that deliver reactive sulfur species in a controllable manner has played an important role in understanding the different roles of various sulfur species. In this review, we focus on three types of sulfur species, including persulfide, SO 2 , and CS 2 . Starting with a brief introduction of their physiological functions, we will then assess the various drug delivery strategies to generate persulfide species, SO 2 , and CS 2 as research tools and potentially as therapeutic agents. Future Directions: Development of donors of various sulfur species that respond to distinct stimulus is critical for this field. Another key to the long-term success of this field is the identification of an area of unmet medical need that can be addressed with these sulfur species.