The addition of chalcone and amine components into indirubin-3′-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e, 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3β enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3β with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3β enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.

在靛玉红3'-肟中加入查尔酮和胺成分，得到15种高收率的新衍生物。还通过1D，2D-NMR和HR-MS（ESI）光谱以及X射线晶体学阐明了新衍生物的结构。筛选所有设计的化合物对四种人类癌细胞系（HepG2，LU-1，SW480和HL-60）和一种人类正常肾细胞系（HEK-293）的细胞毒活性。化合物6f表现出最明显的细胞毒性，同时化合物6e，6h和6l的细胞毒性对癌细胞系比对正常细胞更为深刻。通过对GSK-3β酶的分子对接研究进一步分析了这些新衍生物。对接分析表明，大多数衍生物对结合位点具有特征性相互作用残基的GSK-3β均表现出潜在的抑制活性。然后采用快速拉动配体方案来完善配体与GSK-3β酶之间的结合亲和力和机理。预期计算结果将有助于预测试验抑制剂的酶靶及其可能的相互作用，从而可以在将来创建新的细胞毒剂的设计。