Synthesis and biological activity of mycophenolic acid-amino acid derivatives

• Amino acid MPA derivatives are IMPDH inhibitors.
• Activity depends both on configuration and substituent R in amino acid unit.
• Hydrolysis of methyl esters to free carboxylic group increases activity.
• Three obtained amino acid MPA derivatives gave better in vitro activity than MPA itself.

In search of new immunosuppressants we synthesized 11 amino acids derivatives of MPA as methyl esters 10a–k using EDCI/DMAP and their corresponding amino acid derivatives in free acid form 11a–k by hydrolysis of ester group with LiOH/MeOH. New analogs were evaluated as growth inhibitors of lymphoid cell line (Jurkat) and human peripheral blood mononuclear cells (PBMC) from healthy donors. According to obtained results recovering of free carboxylic group increased their activity. Additionally, the cytotoxic properties depends on the substituent and configuration at chiral center in amino acid unit. The compounds 10j, 11e and 11h exhibited higher potency than MPA 1in vitro.

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