title: Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents.
abstract: 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 N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(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 in vitro 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 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.
authors: a Department of Organic Chemistry , Gdansk University of Technology , Gdansk , Poland and.
authors: Grzegorz
authors: G
authors: Cholewinski
authors: a Department of Organic Chemistry , Gdansk University of Technology , Gdansk , Poland and.
authors: Dorota
authors: D
authors: Iwaszkiewicz-Grzes
authors: b Department of Clinical Immunology and Transplantology , Medical University of Gdansk , Gdansk , Poland.
authors: Piotr
authors: P
authors: Trzonkowski
authors: a Department of Organic Chemistry , Gdansk University of Technology , Gdansk , Poland and.
authors: Krystyna
authors: K
authors: Dzierzbicka
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D054831:Acridones / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D054831:Acridones; D004952:Esters; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Acridines; IMPDH inhibitors; acridones; esterification; mycophenolic acid