Synthesis Of Indirubin Analogues And Anti-tumor Activity Research

Indirubin is the active ingredient of Danggui Longhui Wan, amixture of plants that is used in traditional Chinese medicine to treatchronic myelocytic leukemia effectively. Indirubin derivatives inhibitkinases selectively, including cyclin-dependent kinases and glycogensynthase kinase-3, by binding themselves to them mainly throughhydrogen bonds, thus inducing cell apoptosis.Based on structure-activity relationships of indirubin analogues,twenty-seven target compounds, including3-(3′-oxobenzo[b]thiophen-2′(3′H)-ylidene)indolin-2-ones,3-(3′-oxobenzo[b]thiophen-2′(3′H)-ylide-ne)-1H-pyrrolo[2,3-b]pyridin-2(3H)-ones and2′-(2-oxoindolin-3-ylide-ne)thieno[2,3-b]pyridin-3′(2′H)-ones, were designed and synthesized,twenty-five of which were not reported in the scientific literature. Thestructures of all the target compounds were identified by1H-NMR, IRand ESI-MS.The in vitro anti-tumor activities of twenty-four target compoundswere preliminarily investigated by sulforhodamine B assay. The resultsindicated that most of target compounds showed potent anti-proliferative activities against several human cancer cell lines. The anti-proliferativeeffect of2′-(2-oxoindolin-3-ylidene)thieno[2,3-b]pyridin-3′(2′H)-one onfour human cancer cell lines, including human hepatoma cell lineQGY-7701, human lung cancer cell line A-549, human cervicalcarcinoma cell line HELA and human gastric cancer cell line SGC-7901,was comparable with that of the positive control6-bromoindirubin-3′-oxime.1-Methyl-3-(3′-oxobenzo[b]thiophen-2′(3′H)-ylidene)-1H-pyrro-lo[2,3-b]pyridin-2(3H)-one inhibited the proliferation of these four cancerlines selectively and did not affect the proliferation of normal humanvascular smooth muscle cell line SMC remarkably.These researches lay the certain foundation for the further designand synthesis of indirubin analogues with high efficiency and lowtoxicity.