THE CYTOTOXICITY OF 3-IMINO-1-OXOISOINDOLINES IN MURINE AND HUMAN TISSUE-CULTURE CELLS

Certain types of hypolipidemic agents have been observed to also funct ion as cytotoxic agents. Previously reported hypolipidemic agents, 3-i mino-1-oxoisoindolines, were evaluated for their anti-neoplastic activ ity. Selected agents were effective at inhibiting L1210, Tmolt(3), HeL a-S-3, 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 s ite of inhibition was the purine pathway at IMP dehydrogenase. Other e nzyme 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).