THE CYTOTOXICITY OF N-SUBSTITUTED DIPHENIMIDES AND 6,7-DIHYDRO-5H-DIBENZ[C,E]AZEPINES

N-substituted diphenimides and 6,7-dihydro-5H-dibenz[c,e]azepines demo nstrated significant cytotoxic activity against the growth of murine a nd human cells. These derivatives were active against leukemias, carci nomas and sarcomas. Different derivatives with N-substitutions showed specific activity against the growth of several tumor types. These age nts inhibited L1210 leukemia IMP dehydrogenase and PRPP amido transfer ase activities; this was reflected in the inhibition of purine and DNA synthesis. Other sites inhibited to a minor degree by these agents in cluded DNA polymerase alpha, r- and tRNA polymerases, ribonucleoside r eductase, dihydrofolate reductase, pyrimidine synthesis, and nucleosid e kinase. d(NTP) pool levels' were reduced after 24h incubation with t hese derivatives. L1210 DNA strand scission was evident after drug tre atment.