3-取代氧化吲哚的合成及其抗肿瘤活性研究

The Synthesis and Anti-Tumor Activity of 3-Substituted Oxindoles

以不同取代的靛红为起始原料,通过和各种取代基的格式试剂反应生成3-羟基化氧化吲哚中间体,然后在氮原子和氧原子上用Boc保护,再在Pd/C条件下氢气脱OBoc,即得到3-取代-N-叔丁氧羰基氧化吲哚(3a^3g),总产率为52%~67%,讨论了底物取代基对反应产率的影响。结构经1H NMR,13C NMR和HRMS表征。采用MTT法研究了3a^3g体外对前列腺癌细胞(PC-3)的抗肿瘤活性。结果表明:5-氟-3-苯基-N-叔丁氧羰基氧化吲哚(3d)对PC-3具有较好的抑制活性。

The paper starts with the different substituted isatins reaction with different Grignard reagent to get 3- hydroxymethyl-oxindole intermediates, then introduces the Boc as protection group in the nitrogen and oxygen at- oms, eliminates the OBoe through reaction with hydrogen under the condition of Pd/C, finally to obtain the 3- monosubstituted oxindole（3a-3g）, the yields were 52% -67%, the effects of different substrates were also discussed. All the ultimate compounds were confirmed by 1H NMR and 13C NMR. The compounds＇ antineo- plastic activity was valuated for cytotoxicity against human prostatic cancer cell（ PC-3 ） by MTT method. The re- sults demonstrated that these compounds had the activity of inhibition on the PC-3 cancer cells, especially 3d possessed higher anti-tumor activity.