title: Synthesis and biological activity of mycophenolic acid-amino acid derivatives.
abstract: 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 1 in vitro.
authors.affiliation: Department of Organic Chemistry, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Iwaszkiewicz-Grzes
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Cholewinski
authors.forename: Agata
authors.initials: A
authors.lastname: Kot-Wasik
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dzierzbicka
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D009173:Mycophenolic Acid
keywords: Amino acid derivatives; Cytotoxic activity; IMPDH inhibitors; Mycophenolic acid derivatives