Background: Immunosuppressive drugs are widely used to prevent and treat allograft rejection
and autoimmune diseases. Mycophenolic acid (MPA) and its derivatives are currently one of
the most prescribed immunosuppressive drugs; however, metabolic drawbacks and variable interand
intrapatient responses limit their use.
Objective: In order to find out new safe and effective immunosuppressive compounds, we report
here the synthesis and pharmacological evaluation of hybrid MPA derivatives containing the thalidomide/
Results: All compounds 3a-d exhibited an enhanced ability to reduce the levels of pro-inflammatory
cytokines compared to the parental drugs MPA and thalidomide. The mixed lymphocyte reaction assay
has demonstrated that compound 3d - (E)-(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-
enoate – has superior activity compared to that of MPA. In addition, compound 3d was less cytotoxic
against Jurkat cells than MPA and did not demonstrate in vivo genotoxic effect.
Conclusion: All these data have shown that compound 3d is a promising lead compound useful in
the immunosuppressive therapy.