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Asymmetric synthesis of tetrahydroisoquinoline-fused spirooxindoles as Ras-GTP inhibitors that inhibit colon adenocarcinoma cell proliferation and invasion
- Zhao, Qian, Peng, Cheng, Huang, Hua, Liu, Shuai-Jiang, Zhong, Ya-Jun, Huang, Wei, He, Gu, Han, Bo
- Chemical communications 2018 v.54 no.60 pp. 8359-8362
- apoptosis, cell proliferation, chemical compounds, chemical reactions, colorectal neoplasms, mitochondria, mitogen-activated protein kinase, neoplasm cells
- Here we report the synthesis of a library of chiral THIQ-fused spirooxindoles, which combine two privileged scaffolds in antitumor medicinal chemistry. Some of the library members inhibit the proliferation and invasion ability of Ras-mutated colon adenocarcinoma cells. Mechanistic studies suggest that the most potent compound, 3m, inhibits Ras-GTP and thereby suppresses downstream signaling mediated by MAPK, PI3K-Akt and Wnt. Ultimately this leads to mitochondrial apoptosis.