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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs.
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Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs.

机译：鞘氨醇激酶抑制剂及其新型阿司匹林共轭类似物的合成和生物活性。

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摘要

Sphingosine kinase (SphK) is a lipid kinase with oncogenic activity, and SphK inhibitors (SKIs) are known for their anti-cancer activity. Here, we report highly efficient syntheses of SKIs and their aspirinyl (Asp) analogs. Both SKIs and their Asp analogs were highly cytotoxic towards multiple human cancer cell lines; in several cases the Asp analogs were up to three times more effective. Furthermore, they were equally potent inhibitors of SphK. The pharmacokinetic study indicated that SKI-I-Asp cleaved efficiently to form SKI-I and the half-life of SKI-I was increased from approximately 7 h in SKI-I to approximately 10 h in SKI-I-Asp injected mice, thereby prolonging its effect. In summary, the Asp-conjugated SKIs seem to be promising prodrugs of SKIs where delivery in vivo remains a problem.
机译：鞘氨醇激酶（SphK）是具有致癌活性的脂质激酶，并且SphK抑制剂（SKIs）具有抗癌活性。在这里，我们报告了SKI及其阿司匹林（Asp）类似物的高效合成。 SKI及其Asp类似物对多种人类癌细胞系均具有高度的细胞毒性。在某些情况下，Asp类似物的功效高达三倍。此外，它们同样是SphK的有效抑制剂。药代动力学研究表明，SKI-1-Asp有效裂解形成SKI-1，SKI-1的半衰期从注射SKI-1的大约7小时增加到注射SKI-1-Asp的小鼠大约10小时，从而延长其效果。总之，结合Asp的SKI似乎是有希望的SKI的前药，其中体内递送仍然是一个问题。

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