Hall I H, Wong O T
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill 27599.
Anticancer Drugs. 1994 Apr;5(2):207-12. doi: 10.1097/00001813-199404000-00012.
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).
已观察到某些类型的降血脂药物也具有细胞毒性作用。对先前报道的降血脂药物3-亚氨基-1-氧代异吲哚啉进行了抗肿瘤活性评估。所选药物对抑制L1210、Tmolt3、HeLa-S3、KB鼻咽癌、肺癌、骨肉瘤和神经胶质瘤的生长有效。该类药物的代表性化合物2-丙基-3-亚氨基-1-氧代异吲哚啉（4）抑制L1210细胞的DNA和RNA合成。抑制的主要位点是肌苷酸脱氢酶处的嘌呤途径。受（4）轻微影响的其他酶位点是t-RNA和r-RNA聚合酶、二氢叶酸还原酶、天冬氨酸转羧酶和核苷激酶。用（4）孵育60分钟后，L1210细胞的d（NTP）池减少。
