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DOI: 10.1055/s-0035-1560603
Synthesis of Amino-ADT Provides Access to Hydrolytically Stable Amide-Coupled Hydrogen Sulfide Releasing Drug Targets
Publication History
Received: 05 January 2016
Accepted: 20 January 2016
Publication Date:
04 February 2016 (online)
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Abstract
As additional physiological functions of hydrogen sulfide (H2S) are discovered, developing practical methods for exogenous H2S delivery is important. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) functionalized with H2S-releasing anethole dithiolethione (ADT-OH) through ester bonds are being investigated for their combined anti-inflammatory and antioxidant potential. The chemical robustness of the connection between drug and H2S-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 (ADT-NH2 ) and provide conditions for successful ADT-NH2 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.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560603.
- Supporting Information
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References and Notes
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