| Summary: | 碩士 === 東海大學 === 化學系 === 104 === Src protein is a non-receptor tyrosine kinase and it plays a critical role in cell adhesion, invasion, proliferation, survival, and angiogenesis during tumor development. It was also found to be over-expressed and highly activated in a wide variety of human cancers, including lung, breast, prostate, colon and pancreatic cancer. In an effort to search for efficacious Src inhibitors, both in silico and in vitro screening were performed. We synthesized two compounds, WY1311 and WY1312, screened from computer docking with Src protein, but found no Src inhibition at 10 μM against A549 cell line. In the in vitro screening, digoxigenin suppressed A549 cell progression and inhibited Src activation, we therefore designed and synthesized a series of indole and indoline derivatives based on its structure. Within the derivatives, WY1339 exhibited a good cytotoxicity against A549 cell with a CC50 of 1.98 μM in 24 hours. We also found that the bulky substitution on pyrrolidine-2,5-dione of WY1330 and methoxy group of WY1332 played a key role on bioactivity of A549 cell.
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