发现新型 N-酰腙衍生物作为 Sirtuin-1 的强效抑制剂

IF 2 Q2 CHEMISTRY, ORGANIC
SynOpen Pub Date : 2024-04-04 DOI:10.1055/s-0043-1763747
Victoria V. Lipson, Fedyr G. Yaremenko, Volodymyr M. Vakula, Svitlana V. Kovalenko, Alexander V. Kyrychenko, Sergiy M. Desenko, Petro О. Borysko, Sergiy O. Zozulya
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引用次数: 0

摘要

SIRT1 酶是沉默信息调节因子(Sirtuins)家族的一个重要成员,能催化蛋白质的去乙酰化。因此,开发新的 SIRT1 抑制剂在治疗癌症和与年龄相关的代谢紊乱方面具有潜在的应用价值。在这项研究中,我们合成了一系列 N-酰腙(NAH)衍生物,并通过发光测定法对它们对重组 SIRT1 蛋白的抑制活性进行了高通量筛选。我们通过硅学筛选,发现了一种新的 NAH 衍生物,它对 SIRT1 的活性口袋具有选择性和高结合亲和力,可与 Ex527 和 Sirtinol 等已知抑制剂相媲美。这种高结合亲和力使新衍生物有望成为现有抑制剂的替代品,并有望开发出更好的针对 SIRT1 活性的靶向药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Discovery of Novel N-Acylhydrazone Derivatives as Potent Inhibitors of Sirtuin-1

SIRT1 enzyme is a key family member of Silent Information Regulators (Sirtuins), which catalyze the deacetylation of proteins. Therefore, developing new SIRT1 inhibitors has potential application in treating cancer disease and age-related metabolic disorders. In this study, we synthesized a series of N-acylhydrazone (NAH) derivatives and performed high-throughput screening of their inhibitory activity against the recombinant SIRT1 protein by a luminescent assay. Using in silico screening, we identified a new NAH derivative that features both selectivity and a high binding affinity towards the active pocket of SIRT1 that are comparable to known inhibitors such as Ex527 and Sirtinol. Such high binding affinity makes the new derivatives promising alternatives to the available inhibitors and holds promise for developing better-targeted drugs against SIRT1 activity.

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来源期刊
SynOpen
SynOpen CHEMISTRY, ORGANIC-
CiteScore
2.30
自引率
4.00%
发文量
35
审稿时长
6 weeks
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