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Wyświetlanie 1-1 z 1
Tytuł:
Synthesis and biological activity of raltitrexed-carrier conjugates
Autorzy:
Jagiello, Monika
Kanska, Urszula
Nevozhay, Dmitry
Boratynski, Janusz
Powiązania:
https://bibliotekanauki.pl/articles/1040427.pdf
Data publikacji:
2010
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
raltitrexed
tomudex
carrier
conjugate
thymidylate synthase
Opis:
Drugs used in chemotherapy give undesirable side effects, e.g., cardiotoxicity, leucopenia, hair loss and others. Covalent binding of a drug with a carrier may change its biodistribution, elimination and/or rate of transformation in the organism. The aim of this work was to synthesize conjugates of anticancer drug - raltitrexed (RTX) with lysozyme, bovine serum albumin (BSA), and dextran T40 and to investigate their cytotoxicity and influence on the cell cycle in comparison with the free drug. Before conjugation RTX was transformed into anhydride by treatment with dicyclohexylcarbodiimide in dimethylformamide. Activated RTX was added into aqueous solution of carriers at different pH (from 8.5 to 10.5) for 3 to 15 min. The reaction was stopped by reducing the pH to 7.0. Maximum yield of the reaction was obtained at pH 10 for BSA as well as for dextran. The highest level of substitution was obtained after 5 min of the reaction. In in vitro experiments on three cell lines: SW707, LoVo and A549, all conjugates tested had up to a few hundred times higher IC50 than the free drug. Interestingly, it was noticed that the conjugates based on dextran and albumin were more cytotoxic than the free drug in the highest concentrations tested (1000 and 10000 ng/ml). The influence of RTX and the conjugates on SW707 cell cycle was studied. RTX blocked the cell cycle mostly in the G0-G1 and S phase and increased the percentage of apoptotic cells. Cells in the G2-M phase were not observed. The conjugates blocked the cell cycle in the S phase and decreased the percentage of cells in the G0-G1 phase.
Źródło:
Acta Biochimica Polonica; 2010, 57, 1; 83-87
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
    Wyświetlanie 1-1 z 1

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