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  • Title: The cytotoxicity of 2-formyl and 2-acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II) complexes.
    Author: Miller MC, Bastow KF, Stineman CN, Vance JR, Song SC, West DX, Hall IH.
    Journal: Arch Pharm (Weinheim); 1998 Apr; 331(4):121-7. PubMed ID: 9648520.
    Abstract:
    2-Acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II) complexes were shown to be potent antineoplastic and cytotoxic agents against murine and human cultured cells. Numerous derivatives were as active against solid tumor growth as clinically useful agents. The agents inhibited L1210 DNA and RNA syntheses with inhibition of key regulatory enzyme activities of the purine pathway as well as nucleoside kinase activities. d[NTP] pools were reduced and DNA strand scission occurred. These agents were DNA topoisomerase II inhibitors with lower IC50 values than that of VP-16. However, they did not cause L1210 DNA protein linked breaks and actually protected against those breaks afforded by VP-16. The agents were not synergistic with VP-16 in reducing cell growth or DNA synthesis although they did reduce growth of L1210 cells in agar suspended media.
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