多甲氧基咔唑类似物的合成及其体外抗肿瘤活性
[Synthesis and in vitro antitumor activity of multi-methoxyl carbazole analogues].
作者信息
Zhai Fu-min, You Qi-dong, Wang Hua, Chen Xiao-guang, Li Yan, Li Hong-yan
机构信息
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
出版信息
Yao Xue Xue Bao. 2004 Oct;39(10):808-12.
AIM
To design and synthesize new methoxyl carbazole analogues as antitumor compounds.
METHODS
Methoxyl-nitrobiphenyls (3a-3c) were prepared through the Ullmann reaction of 4,5-dimethoxyl-2-bromonitrobenzene and methoxyl-iodobenzene compounds with the catalysis of copper powder, and then reduced by P(EtO)3 to obtain methoxyl carbazoles 4a-4c. The modification at 9-position of the methoxyl carbazoles (4a-4c) gives 16 carbazole derivatives (5a-5p). These compounds were confirmed by 1HNMR, MS, IR and elemental analysis.
RESULT
In vitro antitumor activities evaluation in vitro demonstrated that IC50 value of the target compounds 4c, 5a, 5b, 5g, 5h, 5i, 5l, 5n and 5p against HT-29 cells were 12.1, 10.6, 8.1, 3.1, 4.4, 10.1 and 9.2 micromol x L(-1) respectively, and IC50 value of the target compound 4a against KB was 17.7 micromol x L(-1).
CONCLUSION
Some of the target compounds have better inhibitory effects against H-29 and KB cells.
目的
设计并合成新型甲氧基咔唑类似物作为抗肿瘤化合物。
方法
以4,5-二甲氧基-2-溴硝基苯和甲氧基碘苯化合物为原料，在铜粉催化下通过乌尔曼反应制备甲氧基硝基联苯（3a - 3c），然后用三乙基亚磷酸酯还原得到甲氧基咔唑4a - 4c。对甲氧基咔唑（4a - 4c）的9位进行修饰得到16个咔唑衍生物（5a - 5p）。这些化合物通过1HNMR、MS、IR和元素分析进行确证。
结果
体外抗肿瘤活性评价表明，目标化合物4c、5a、5b、5g、5h、5i、5l、5n和5p对HT - 29细胞的IC50值分别为12.1、10.6、8.1、3.1、4.4、10.1和9.2微摩尔·升-1，目标化合物4a对KB细胞的IC50值为17.7微摩尔·升-1。
结论
部分目标化合物对H - 29和KB细胞具有较好的抑制作用。
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