2016/02/04 by Michael Pluth, Michael D. Pluth, Matthew D. Hammers +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Sulfur Compounds in Biology #Mast cells and histamine #Asthma and respiratory diseases
paper · doi:10.1055/s-0035-1560603
As additional physiological functions of hydrogen sulfide (H<sub>2</sub>S) are discovered, developing practical methods for exogenous H<sub>2</sub>S delivery is important. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) functionalized with H<sub>2</sub>S-releasing anethole dithiolethione (<b>ADT-OH</b>) through ester bonds are being investigated for their combined anti-inflammatory and antioxidant potential. The chemical robustness of the connection between drug and H<sub>2</sub>S-delivery components, however, is a key and controllable linkage in these compounds. Because esters are susceptible to hydrolysis, particularly under acidic conditions such as stomach acid in oral drug delivery applications, we report here a simple synthesis of amino-ADT (<b>ADT-NH<sub>2</sub> </b>) and provide conditions for successful <b>ADT-NH<sub>2</sub> </b> derivatization with the drugs naproxen and valproic acid. Using UV-vis spectroscopy and HPLC analysis, we demonstrate that amide-functionalized ADT derivatives are significantly more resistant to hydrolysis than ester-functionalized ADT derivatives.