The cytotoxicity of 3-imino-1-oxoisoindolines in murine and human tissue culture cells.
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).
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Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill 27599.
Wong
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007211:Indoles; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm