N_(12)-乙基取代吲哚咔唑衍生物的合成及细胞毒活性研究

Synthesis and Cytotoxicity of N_(12)-Ethyl Substituted Indolocarbazole Derivatives

合成了9个新的N12-乙基取代吲哚咔唑衍生物6~14,其结构经1H NMR、13C NMR和HRESIMS确定.用噻唑蓝（MTT）法测试了衍生物对人肺癌细胞A549、肝癌细胞Hep G-2和宫颈癌细胞Hela的细胞毒活性.用细胞计数试剂盒-8（Cell Counting Kit-8,CCK-8）法测试了衍生物对白血病细胞K562的细胞毒活性.结果显示,化合物7~9对K562的细胞毒活性与阳性对照阿霉素（ADM）相近,半数抑制浓度（IC50）为0.43~0.93μmol/L.化合物8和12对Hela的活性与阳性对照相近,IC50分别为1.23和0.43μmol/L.化合物13的盐酸盐14对所测试的4种肿瘤细胞株均有较强的抑制活性,IC50值在0.23~1.72μmol/L之间,可作为抗肿瘤先导化合物进行深入研究.

Nine new N12-ethyl substituted indolocarbazole derivatives were synthesized. Their structures were identified by 1H NMR, 13C NMR and HRESIMS. The thiazolyl blue tetrazolium bromide （MTT） method was used to evaluate the cytotoxicities of these derivatives against A549, HepG-2 and Hela cell lines, while the cell counting kit-8 （CCK-8） method was used to evaluate cytotoxicity against K562 cell lines. The results showed that compounds 7-9 displayed comparable cytotoxicity to adriamycin （ADM） against K562 cell lines with the ICs0 values of0.43-0.93 μmol/L. Compounds 8 and 12 showed comparable cytotoxicity to ADM against Hela cell lines with the IC50 values of 1.23 and 0.43 μmol/L, respectively. The hydrochloride 14 of compound 13 exhibited good cytotoxicity against the four cell lines with the IC50 values of 0.23 - 1.72 μmol/L, indicating a worth of further study as an antitumor lead compound.