Design and Catalyzed Activation of Mycophenolic Acid Prodrugs.

ABSTRACT: Mycophenolic acid (MPA) and its morpholino ester prodrug mycophenolate mofetil (MMF) are widely used in solid organ transplantation. These drugs prevent rejection due to their potent inhibition of inosine-5'-monophosphate dehydrogenase (IMPDH), an enzyme vital for lymphocyte proliferation. As a strategy to provide localized immunosuppression in cell transplantation, four mycophenolic acid prodrugs designed to release MPA by two distinct mechanisms were synthesized and characterized. A nitrobenzyl ether prodrug was effectively converted to MPA upon exposure to bacterial nitroreductase, while a propargyl ether was converted to the active drug by immobilized Pd⁰ nanoparticles. In vitro, both prodrugs were inactive against IMPDH and exhibited reduced toxicity relative to the

SUBMITTER: Plunk MA 

PROVIDER: S-EPMC8155237 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature