Sulfur dioxide prodrugs: triggered release of SO₂via a click reaction

Abstract

Sulfur dioxide (SO2) is being recognized as a possible endogenous gasotransmitter with importance on par with that of NO, CO, and H2S. Herein we describe a series of SO2 prodrugs that are activated for SO2 release via a bioorthogonal click reaction. The release rate can be tuned by adjusting the substituents on the prodrug.

Organic CO Prodrugs: Structure–CO‐Release Rate Relationship Studies

“…[12c] Briefly, compound 1a–b were condensed with a variety of alcohol or amine to afford compounds 2a–i , which were found to exist as a mixture of keto-enol tautomers (Scheme 1). Compounds 2a–i were then reacted with acenaphthylene-1,2-dione, followed by treatment with an acid for dehydration to yield the desired CO prodrugs BW-CO-104-106 , and 108-113 in 20–77% yield.…”

“…[12c] Cytotoxicity of the other CO prodrugs along with their corresponding products after CO release was studied in Raw 264.7 cells with a drug exposure time of 24 h. The results (Figure S18–19) revealed that most of the compounds tested did not present obvious cytotoxicity at 100 μM, and only a few CO prodrugs ( BW-CO-112, 113, 115, 116, 120 and 121 ) and inactive products ( BW-CP-111/115/120 ) showed cytotoxicity with IC 50 values in the range of 50–100 μM. Clearly, there is no general intrinsic toxicity issues related to this class of compounds, but idiosyncratic toxicity may occur with individual compounds, which can also be addressed by structural optimizations.…”

“…The reported “Two compartment” myoglobin-CO assay system was employed here. [12c] A myoglobin solution in PBS (0.01 M, pH = 7.4) (1.7 mg/mL, 2.9 mL) was degassed by bubbling with nitrogen for at least 20 min and a freshly prepared solution of sodium dithionite (17mg/mL, 300 μL) was added to the myoglobin solution. Then the CO prodrug (1 mM) was added to the inner vial.…”

“…[7, 11–12] Recently, we have disclosed the first class of CO-prodrugs that can release CO under physiological condition. [12c] Such CO prodrugs can spontaneously release CO upon dissolution in a mixed aqueous solution or in a biological medium, and generate a fluorescent reporter after CO release (Figure 1, Scaffold I). Most importantly, they showed very pronounced anti-inflammatory effects in Raw 264.7 cells.…”

Redox‐guided small molecule antimycobacterials

“…These compounds were shown to permeate S. aureus , deplete intracellular thiols and induce oxidative stress. While a number of other SO 2 donors were developed, their antibacterial properties are not reported . Together, these SO 2 donors offer unique possibilities for further development if toxicity issues can be sorted out.…”