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  • Title: Cytotoxicity of 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and mode of action in human Tmolt4 cells.
    Author: Hall IH, Barnes BJ, Rowell JE, Shaffer KA, Cho SE, West DX, Stark AM.
    Journal: Pharmazie; 2001 Aug; 56(8):648-53. PubMed ID: 11534344.
    Abstract:
    The 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and their copper complexes demonstrated potent cytotoxic activity against a series of murine and human suspended cultured tumor cells. Selected compounds were active against the growth of cultured cells from solid human tumors, i.e. Mck-7 breast effusion, lung A549 and lung MB-9812, bone SOS-2 and clear cell Caki renal tumor. In Tmolt4 T cell leukemia cells the compounds inhibited the syntheses of DNA, RNA and protein over 60 min at 25 to 100 microM. Multiple target sites in nucleic acid metabolism were suppressed by the agents, i.e. DNA polymerase alpha, ribonucleoside reductase, dihydrofolate reductase, de novo purine synthesis, thymidylate synthetase and nucleoside kinases. The total effects of the agents on DNA metabolism led to the reduction of deoxyribonucleotide pools as well as DNA fragmentation.
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