The cytotoxicity of N-substituted indazolones in murine and human tumor cells.

N-Substituted indazolones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt3, colon adenocarcinoma and HeLa-S3. Selected agents were also active against the growth of KB, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of L1210 cells, which reduces DNA and RNA syntheses. Agents lowered d(NTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with N-substituted indazolones for 24 h at 100 microM, lowering DNA synthesis and causing cell death.