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目的合成具有新结构骨架的含氮姜黄素类抗肿瘤化合物并考察目标化合物的体外抗肿瘤活性。方法以姜黄素和查耳酮为先导物,利用药效团和骨架迁越原理,设计并合成一系列含碱基的姜黄素类似物。选取人肺癌细胞(A-549)和人胃癌细胞(SGC-7901)对所合成的新化合物进行体外抗肿瘤活性筛选。并且用Discovery Studio 2.0软件进行化合物的吸收、分布、代谢和排泄(ADME)预测。结果与结论共合成了15个未见文献报道的新化合物,其结构均经MS(ESI)、1H-NMR确证。体外活性筛选结果表明:所合成的化合物对所测的两种肿瘤细胞的活性明显优于姜黄素。ADME预测结果表明:所合成的化合物都可能在体内被很好地吸收,血浆蛋白结合率较姜黄素有较大提高。
OBJECTIVE: To synthesize the antitumor compounds of nitrogen-containing curcuminoids with new structural skeleton and investigate the antitumor activity of the target compounds in vitro. Methods Using curcumin and chalcone as precursors, a series of base-containing curcumin analogs were designed and synthesized by using pharmacophore and framework migration theory. In vitro antitumor activity screening of the new compounds was performed by selecting human lung cancer cells (A-549) and human gastric cancer cells (SGC-7901). And the absorption, distribution, metabolism and excretion (ADME) prediction of compounds using Discovery Studio 2.0 software. RESULTS AND CONCLUSIONS A total of 15 new compounds were synthesized and their structures were confirmed by MS (ESI) and 1H-NMR. In vitro activity screening results show that: the compounds synthesized by the measured activity of two tumor cells was significantly better than curcumin. ADME predictions show that all the compounds synthesized may be well absorbed in the body and the plasma protein binding rate is greatly increased compared with that of curcumin.