Hall I H, Wong O T, Chi L K
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27559-7360.
Anticancer Drugs. 1993 Dec;4(6):665-70. doi: 10.1097/00001813-199312000-00009.
N-substituted diphenimides and 6,7-dihydro-5H-dibenz[c,e]azepines demonstrated significant cytotoxic activity against the growth of murine and human cells. These derivatives were active against leukemias, carcinomas and sarcomas. Different derivatives with N-substitutions showed specific activity against the growth of several tumor types. These agents inhibited L1210 leukemia IMP dehydrogenase and PRPP amido transferase activities; this was reflected in the inhibition of purine and DNA synthesis. Other sites inhibited to a minor degree by these agents included DNA polymerase alpha, r- and tRNA polymerases, ribonucleoside reductase, dihydrofolate reductase, pyrimidine synthesis, and nucleoside kinase. d(NTP) pool levels were reduced after 24 h incubation with these derivatives. L1210 DNA strand scission was evident after drug treatment.
N-取代二苯甲酰亚胺和6,7-二氢-5H-二苯并[c,e]氮杂卓对小鼠和人类细胞的生长表现出显著的细胞毒性活性。这些衍生物对白血病、癌和肉瘤具有活性。具有N-取代的不同衍生物对几种肿瘤类型的生长表现出特异性活性。这些药物抑制L1210白血病IMP脱氢酶和PRPP酰胺转移酶活性；这反映在嘌呤和DNA合成的抑制上。这些药物在较小程度上抑制的其他位点包括DNA聚合酶α、r-和tRNA聚合酶、核糖核苷还原酶、二氢叶酸还原酶、嘧啶合成和核苷激酶。与这些衍生物孵育24小时后，d(NTP)池水平降低。药物处理后L1210 DNA链断裂明显。
