Synthesis and biochemical evaluation of Δ2-isoxazoline derivatives as DNA methyltransferase 1 inhibitors

…, F López-Vallejo, P Conti, L Tamborini…

文献索引：Castellano, Sabrina; Kuck, Dirk; Viviano, Monica; Yoo, Jakyung; Lopez-Vallejo, Fabian; Conti, Paola; Tamborini, Lucia; Pinto, Andrea; Medina-Franco, Jose L.; Sbardella, Gianluca Journal of Medicinal Chemistry, 2011 , vol. 54, # 21 p. 7663 - 7677

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被引用次数: 63

摘要

A series of Δ2-isoxazoline constrained analogues of procaine/procainamide (7a–k and 8a– k) were prepared and their inhibitory activity against DNA methyltransferase 1 (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC50= 150 μM) than other non- nucleoside inhibitors and also exhibits a strong and dose-dependent antiproliferative effect against HCT116 human colon carcinoma cells. The binding mode of 7b with the enzyme ...