Tunable Hydrogen Sulfide Drugs

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Introduction: Despite its reputation as a colorless and toxic gas at high concentrations, hydrogen sulfide (H2S) plays an important role as an endogenous signaling molecule in mammals. Therefore, H2S has promising medical and pharmaceutical applications. Hydrogen sulfide has been shown to have anti-inflammation, anti-tumor, cardiovascular protection, and antioxidation effects. However, one major challenge in the development of H2S-based therapeutics is its delivery. There is an unmet need to develop a method to deliver H2S with precisely controlled doses and release rates. Technology: Georgia State University researchers developed an improved method to release hydrogen sulfide through a lactonization reaction under in-vivo conditions. Prodrugs generated through this method can directly release hydrogen sulfide and easily be conjugated to another non-steroidal ani-inflammatory drug (NSAID), leading to the easy synthesis of hybrid prodrugs. Tunable release rates were achieved by modifying the protecting group and the lactonization rate. In-vitro studies have also shown that the prodrugs effectively inhibited cytokine secretion. Conjugating such H2S prodrugs with NSAID could generate many promising therapeutic hybrid drugs.