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I.H. HALL, S.D. WYRICK, C.L. WALLER
Citation:
I.H. HALL, S.D. WYRICK, C.L. WALLER. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/540.
Description:
Substituted oxoisoindolines are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. n general these agents were not active against the solid cell growth, i.e. KB, skin, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. he mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. urine synthesis was reduced by compound 16 at both regulatory enzymes, i.e. PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. he agent lowered D(GTP) and D(CTP) pool levels, further reducing DNA synthesis. NA strand scission was evident after incubation with Compound 16 for 24 hr at 100 uM and some undefined interaction between the drug and the nucleoside bases appeared to occur, lowering DNA synthesis and causing cell death.