THE CYTOTOXICITY OF 2-FORMYL AND 2-ACETYL-(6-PICOLYL)-N-4-SUBSTITUTEDTHIOSEMICARBAZONES AND THEIR COPPER(II) COMPLEXES

2-Acetyl-(6-picolyl)-N-4-substituted thiosemicarbazones and their copp er(II) complexes were shown to be potent antineoplastic and cytotoxic agents against murine and human cultured cells. Numerous derivatives w ere as active against solid tumor growth as clinically useful agents. The agents inhibited L-1210 DNA and RNA syntheses with inhibition of h ey regulatory enzyme activities of the purine pathway as well as nucle oside kinase activities, d[NTP] pools were reduced and DNA strand scis sion occurred. These agents were DNA topoisomerase II inhibitors with lower IC50 values than that of VP-16. However, they did not cause L-12 10 DNA protein linked breaks and actually protected against those brea ks afforded by VP-16. The agents were not synergistic with VP-16 in re ducing cell growth or DNA synthesis although they did reduce growth of L-1210 cells in agar suspended media.