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作为抗癌治疗药物的新型选择性基于醇的素脱乙酶10抑制剂

Amer H Tarawneh¹, Salah A Al-Trawneh^2,3, Talha Z Yesiloglu⁴

¹Department of Chemistry, Faculty of Science, Tafila Technical University, P.O. Box 179, Tafila, 66110, Jordan. amer.tarawneh@ttu.edu.jo.

Scientific reports

|September 26, 2025

概括

新的双循环胺酸被合成为潜在的抗癌剂. 化合物2a强烈抑制了HDAC10,而其他化合物则对HDAC6或IIb类标具有选择性,显示出治疗前景.

科学领域:

药用化学医学化学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
癌症治疗方法癌症治疗方法

背景情况:

基因组脱乙酶 (HDAC) 抑制剂是影响表观遗传和非表观遗传细胞过程的关键抗癌剂.
HDACs调节基因表达,它们的失调与各种癌症有关,使它们成为治疗点.

研究的目的:

合成和评估新型双循环胺酸衍生物作为选择性HDAC抑制剂.
评估这些化合物对I类和IIb类HDAC的抑制活性和选择性.
研究这些化合物对人类固体瘤细胞系和正常脏细胞系的抗增殖作用.

主要方法:

新型双循环胺酸衍生物的合成.
在体外酶分析测试以确定针对特定HDAC异型 (HDAC10,HDAC6,I类) 的IC50值.
分子对接和动力学模拟以了解结合相互作用.
基于细胞的测试,以评估对癌症和正常细胞系的抗增殖活性.

主要成果:

化合物2a显示HDAC10的强烈抑制 (IC50 = 0.41 ± 0.02 nM) 与有利的对接相互作用.
化合物2e选择性地抑制了HDAC10超过HDAC6和I类HDACs.
化合物2f优先抑制了HDAC6 (IC50 = 2.5 ± 0.3 nM). 在这种情况下
化合物2c和2d对IIb类比I类HDACs具有选择性.
化合物对测试的瘤细胞系和对正常脏细胞的选择性表现出不同的抗增殖作用.

结论:

新型双循环胺酸具有强大和选择性的HDAC抑制活性.
化合物2a是HDAC10向癌症治疗的一个有希望的头.
合成的化合物为开发具有减少毒性的选择性抗癌药物提供了潜力.

关键词:

这是一种HDAC10抑制剂.希斯脱乙酶的使用分子对接是分子对接.分子动力学分子动力学瘤细胞系中的瘤细胞系.

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