以6,11-二氢-5H-苯并[a]咔唑优势结构为基础的抑制宫颈癌细胞增殖先导化合物的发现

Discovery of lead compounds to inhibit proliferation of cervical cancer cells based on privileged structure of 6,11-dihydro-5H-benzo[a]carbazole

目的·发现以6,11-二氢-5H-苯并[a]咔唑环为母核可抑制宫颈癌细胞增殖的先导化合物。方法·用Fisher吲哚合成法制备了一系列6,11-二氢-5H-苯并[a]咔唑类化合物及其类似物,并在体外用CCK8法测试了这些化合物对He La细胞增殖的抑制作用。结果·2-甲氧基-6,11-二氢-5H-苯并[a]咔唑和8-氯-2-甲氧基-6,11-二氢-5H-苯并[a]咔唑具有良好的抑制He La细胞增殖的活性,其半数抑制浓度(IC50)值分别为9.61μmol/L和16.52μmol/L。结论·发现2个目标先导化合物。在6,11-二氢-5H-苯并[a]咔唑类衍生物中,母环2位C上为甲氧基取代的衍生物具有较好的抗宫颈癌细胞增殖活性。

Objective·To discover lead compounds with 6,11-dihydro-5H-benzo[a]carbazole as core scaffold that can inhibit the proliferation of cervical cancer cells.Methods·A series of 6,11-dihydro-5H-benzo[a]carbazole derivatives and analogs were synthesized using Fischer indole synthesis method,and their anticancer activity against HeLa cells was tested in vitro by CCK8 test.Results·2-Methoxy-6,11-dihydro-5H-benzo[a]carbazole and 8-chloro-2-methoxy-6,11-dihydro-5H-benzo[a]carbazole could significantly inhibit the proliferation of HeLa cells with the half maximal inhibitory concentration(IC50)values of 9.61μmol/L and 16.52μmol/L,respectively.Conclusion·Two objective lead compounds were found.Among 6,11-dihydro-5H-benzo[a]carbazole derivatives,compounds with methoxy group at the C-2 position of the core scaffold show better activity against proliferation of cervical cancer cells.