Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines
Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines
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DOI：
10.1021/acsmedchemlett.9b00553
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发表时间：
2020-05-14
影响因子：
4.2
通讯作者：
Hanessian, Stephen
中科院分区：
文献类型：
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作者：
Bachollet, Sylvestre P. J. T.;Vece, Vito;Hanessian, Stephen
将与FTY 720的环约束羟甲基吡咯烷类似物相关的合成鞘脂化学修饰以包括一系列烷氧基连接的3，6-取代的1，2-哒嗪，所述FTY 720已知使癌细胞饿死。这些衍生物对来自四种不同癌症类型的八种人类癌细胞系表现出优异的抗增殖活性。相对于缺少附加杂环的先导化合物，在这些细胞系中观察到IC 50降低2.5至9倍。
A synthetic sphingolipid related to a ring constrained hydroxymethyl pyrrolidine analog of FTY720 that was known to starve cancer cells to death was chemically modified to include a series of alkoxy-tethered 3,6-substituted 1,2-pyridazines. These derivatives exhibited excellent antiproliferative activity against eight human cancer cell lines from four different cancer types. A 2.5- to 9-fold reduction in IC50 in these cell lines was observed relative to the lead compound, which lacked the appended heterocycle.