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The cytotoxicity of 3-imino-1-oxoisoindolines in murine and human tissue culture cells
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1994
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Chemoprevention StrategyCell DeathPathologyImp DehydrogenaseGliomaRedox BiologyToxicological MechanismOxidative StressDrug ResistanceMedicinal ChemistryToxicologyAnti-cancer AgentBiochemistryOncogenic AgentReactive Oxygen SpecieExperimental ToxicologyPharmacologyCell BiologyKb NasopharynxNatural SciencesHypolipidemic AgentsMedicine
Certain types of hypolipidemic agents have been observed to also function as cytotoxic agents. Previously reported hypolipidemic agents, 3-imino-1-oxoisoindolines, were evaluated for their anti-neoplastic activity. Selected agents were effective at inhibiting L1210, Tmolt3, HeLa-S3, KB nasopharynx, lung, osteosarcoma and glioma growth. 2-Propyl-3-imino-1-oxoisoindoline, (4), a representative compound of the class of agents, inhibited DNA and RNA syntheses of L1210 cells. The major site of inhibition was the purine pathway at IMP dehydrogenase. Other enzyme sites which were affected by (4) marginally were t-RNA and r-RNA polymerases, dihydrofolate reductase, aspartate transcarboxylase, and nucleoside kinases. d(NTP) pools of L1210 cells were reduced after 60 min. Incubation with (4).