Hall I H, Wong O T, Hall E S, Chen L K
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27559-7360.
Anticancer Drugs. 1993 Jun;4(3):389-93. doi: 10.1097/00001813-199306000-00017.
N-Substituted indazolones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt3, colon adenocarcinoma and HeLa-S3. Selected agents were also active against the growth of KB, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of L1210 cells, which reduces DNA and RNA syntheses. Agents lowered d(NTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with N-substituted indazolones for 24 h at 100 microM, lowering DNA synthesis and causing cell death.
N-取代吲唑酮是有效的细胞毒性剂，可在多种组织培养细胞系中引起细胞死亡，例如L1210、Tmolt3、结肠腺癌和HeLa-S3细胞系。所选药物对KB细胞、支气管源性肺癌、骨肉瘤和神经胶质瘤的生长也有活性。这些衍生物的作用模式包括抑制L1210细胞的嘌呤从头合成，从而减少DNA和RNA的合成。药物降低了d（NTP）库水平，进一步减少了DNA合成。在100微摩尔浓度下与N-取代吲唑酮孵育24小时后，DNA链断裂明显，降低了DNA合成并导致细胞死亡。
