Synthesis of Amino-ADT Provides Access to Hydrolytically Stable Amide-Coupled Hydrogen Sulfide Releasing Drug Targets.
Synthesis of Amino-ADT Provides Access to Hydrolytically Stable Amide-Coupled Hydrogen Sulfide Releasing Drug Targets.
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DOI：
10.1055/s-0035-1560603
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Pluth MD
中科院分区：
文献类型：
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作者：
Hammers MD;Singh L;Montoya LA;Moghaddam AD;Pluth MD
随着硫化氢(H_2S)的额外生理功能被发现，开发实用的外源H_2S输送方法是重要的。特别是，非甾体抗炎药(NSAIDs)通过酯键释放硫化氢的茴香脑二硫代硫酮(ADT-OH)，因其兼具抗炎和抗氧化的潜力而被研究。然而，药物和硫化氢释放组分之间联系的化学稳定性是这些化合物中关键的和可控的联系。由于酯类药物在口服给药过程中易发生水解性反应，特别是在胃酸等酸性条件下，本文报道了一种简单的氨基-氨基转移酶(ADT-NH2)的合成方法，并为ADT-NH2与药物萘普生和丙戊酸的衍生化反应提供了条件。利用UV-Vis光谱和高效液相色谱分析，我们证明了酰胺官能化的ADT衍生物比酯官能化的ADT衍生物具有更强的抗水解性。
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.