Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant,
it also possesses anticancer activity. MPA acts as Inosine-5’-Monophosphate Dehydrogenase
(IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme
via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the
other hand, potent anticancer agents like dacarbazine and cisplatin give numerous side-effects.
Objective: Based on the literature data, MPA derivatives should be explored towards anticancer properties.
Conversion of the carboxylic group of MPA to amide could maintain antiproliferative activity. Therefore, we
decided to investigate several amino acid and peptide derivatives of MPA against chosen cancer cell lines in vitro.
Methods: Amides of MPA hold threonine and arginine amino acid unit. These amino acid derivatives were
tested as L and D enantiomers and both in free acid and methyl esters forms. Additionally, MPA was modified
with tuftsin or retro-tuftsin as biologically active peptides, which could act as a drug carrier.
Results: Amino acid and peptide derivatives of MPA were investigated in vitro as potential anticancer agents on
cell lines: Ab melanoma, A375 melanoma and SHSY5Y neuroblastoma. The activity of the tested compounds
was compared to parent MPA and known chemotherapeutics: dacarbazine and cisplatin.
Conclusion: Amino acid moiety and the sequence of amino acids in the peptide part influenced observed activity.
The most active amino acid MPA analogues occurred to be D and L-threonine derivatives as methyl esters,
probably due to better cell membrane penetration.