DNA binding acridine-thiazolidinone agents affecting intracellular glutathione
| Autor: | Pavol Kristian, Helena Paulíková, Lýdia Čižeková, Slávka Hamuľaková, Mária Kožurková, Zuzana Vantová, Mária Čarná, Danica Sabolová, Ľuba Hunáková, Ján Imrich |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Clinical Biochemistry Pharmaceutical Science HL-60 Cells Biochemistry chemistry.chemical_compound Drug Discovery Cytotoxic T cell Humans Molecular Biology Chemistry Organic Chemistry Glutathione DNA Cell cycle Molecular biology In vitro Intercalating Agents Cell culture Acridine Cancer cell Molecular Medicine Acridines Thiazolidines |
| Zdroj: | Bioorganicmedicinal chemistry. 20(24) |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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