title: Synthesis and biological activity of novel mycophenolic acid conjugates containing nitro-acridine/acridone derivatives.
abstract: Hybrid pharmacophore anti-proliferative compounds, comprised of mycophenolic acid (MPA) and 1-nitroacridine/4-nitroacridone derivative have been synthesized and evaluated as inhibitors of five different leukemia cell lines (Jurkat, Molt-4, HL-60, CCRF-CEM, L1210) and human peripheral blood mononuclear cells from healthy donors. These conjugates possess different length of the linker between MPA and heterocyclic units. The type of heterocyclic part influenced their cytotoxic and anti-proliferative properties. Coupling of MPA 1 with 9-(ω-aminoalkyl)amino-1-nitroacridines 2 and 1-[(ω-aminoalkyl)-4-nitro-9(10H)]-acridones 3 was tested. Although all tested conjugates were active, compounds 4a-e exhibited the highest potency. Preliminary experiments with GMP suggested that the tested compounds acted as IMPDH inhibitors.
authors.affiliation: Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Malachowska-Ugarte
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Cholewinski
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dzierzbicka
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
mesh_terms: D000166:Acridines / Q000737:chemistry*; D054831:Acridones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009173:Mycophenolic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000166:Acridines; D054831:Acridones; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid