title: DNA binding acridine-thiazolidinone agents affecting intracellular glutathione.
abstract: Three new acridine-thiazolidinone derivatives (2a-2c) have been synthesized and their interactions with calf thymus DNA and a number of cell lines (leukemic cells HL-60 and L1210 and human epithelial ovarian cancer cell lines A2780) were studied. The compounds 2a-2c possessed high affinity to calf thymus DNA and their binding constants determined by spectrofluorimetry were in the range of 1.37 × 10(6)-5.89 × 10(6) M(-1). All of the tested derivatives displayed strong cytotoxic activity in vitro, the highest activity in cytotoxic tests was found for 2c with IC(50) = 1.3 ± 0.2 μM (HL-60), 3.1 ± 0.4 μM (L1210), and 7.7 ± 0.5 μM (A2780) after 72 h incubation. The cancer cells accumulated acridine derivatives very fast and the changes of the glutathione level were confirmed. The compounds inhibited proliferation of the cells and induced an arrest of the cell cycle and cell death. Their influence upon cells was associated with their reactivity towards thiols and DNA binding activity.
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Faculty of Chemical and Food Technology, Radlinského 9, SK-81237 Bratislava, Slovak Republic. helena.paulikova@stuba.sk
authors.forename: Helena
authors.initials: H
authors.lastname: Paulíková
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vantová
authors.forename: L'uba
authors.initials: L
authors.lastname: Hunáková
authors.forename: Lýdia
authors.initials: L
authors.lastname: Čižeková
authors.forename: Mária
authors.initials: M
authors.lastname: Čarná
authors.forename: Mária
authors.initials: M
authors.lastname: Kožurková
authors.forename: Danica
authors.initials: D
authors.lastname: Sabolová
authors.forename: Pavol
authors.initials: P
authors.lastname: Kristian
authors.forename: Slávka
authors.initials: S
authors.lastname: Hamul'aková
authors.forename: Ján
authors.initials: J
authors.lastname: Imrich
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000166:Acridines; D007364:Intercalating Agents; D053778:Thiazolidines; D004247:DNA; D005978:Glutathione