Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents

<p>Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with <i>N</i>-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or <i>N</i>-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency <i>in vitro</i> than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives <b>2b, 2d, 3a, 3b</b> displayed the most promising immunosuppressive activity.</p

New conjugates of mycophenolic acid and their antiproliferative activity

<p>The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of <i>N</i>⁶-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds <b>4a–h</b> were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity. The compound <b>4b</b> possessing 1,3-diamine spacer exhibited the most promising results and can be considered to further investigations.</p

Synthesis and antiproliferative activity of new mycophenolic acid conjugates with adenosine derivatives

<p>New conjugates of mycophenolic acid (MPA) and adenosine derivatives were synthesized and assessed as potential immunosuppressants on Jurkat cell line and peripheral blood mononuclear cells (PBMC) from healthy donors. As compared to MPA, all compounds were found to be more active against Jurkat cell line. The antiproliferative activities were compared with MPA and adenosine, in both 2′,3′-<i>O</i>-isopropylidene protected and free hydroxyl groups possessing forms. The obtained results were also discussed in terms of selectivity index, defined as SI = IC₅₀/EC₅₀.</p