Date of Award
Doctor of Philosophy (PhD)
Prodrug is an often-used approach to facilitate the delivery of an active drug to an appropriate site with targeted release whenever possible. Proper prodrug design often relies on a few essential requirements: prodrug stability, triggered release, and selectivity. In the last few decades, there have been impressive progress in prodrug development. However, the delivery of gasotransmitters and ensuring linker stability while allowing drug release at the desired site of action are among remaining challenges. The dissertation work focuses on developing new chemical strategies to address these two issues using hydrogen sulfide (H2S) as a model for gasotransmitters and doxorubicin as a model for anticancer compounds. In the gasotransmiter part of the project, we developed a “trimethyl lock”-lactonization based approach to deliver pure H2S, an esterase-sensitive acetal approach to deliver persulfide, and an enrichment-triggered release method to deliver doxorubicin. The therapeutic effects of these prodrugs were evaluated in a combination of in vitro and in vivo models. The concepts described should be generally applicable and should be very useful to those interested in prodrug design.
Zheng, Yueqin, "New Chemical Strategies for prodrug preparations: from sulfide to doxorubicin." Dissertation, Georgia State University, 2017.