5,6-二取代苯并氧化呋咱类似物的合成与体外抗肿瘤活性研究

Synthesis and Antitumor Activities in vitro of 5,6-Disubstituted Benzofuroxan Analogues

2,4-二氯硝基苯经硝化、胺基取代、叠氮取代和环合四步反应,合成了15个5,6-二取代苯并氧化呋咱类似物,结构均经~1H NMR和HRMS确证.采用SRB法评价了目标物对人非小细胞肺癌细胞NCI H460、结肠癌细胞HCT-116和乳腺癌细胞MCF-7的抑制作用.结果表明,多数目标物(浓度5μmol/L)具有一定的体外抗肿瘤活性,4k、4l和4o对HCT-116的细胞抑制率大于60%,4a、4d、4k、4l和4o对MCF-7细胞的抑制率大于85%.4 o对MCF-7具有显著的抑制活性,IC_(50)为1.6μmol/L.

Fifteen 5,6-disubstituted benzofuroxan analogues are synthesized from 2,4-dichloro-nitrobenzene by the reactions of nitration,amino substitution,azidation and cyclization. Their structures are characterized by I H NMR and HRMS. Their antitumor activities in vitro against NCI H460, MCF-7 and HCT-116 are evaluated by SRB assay. In the preliminary study, it is found that most of the target compounds （5 μmoL/L） show certain extent of inhibition against cancer cells. The inhibition rates of 4k,41 and 4o against colon cancer HCT-116 cells are above 60% ; the inhibition rates of 4a,4d,4k,41 and 4o against breast cancer MCF-7 cells are above 85%. The IC50 of 40 against breast cancer MCF-7 cells is 1.6 μmol/L.