可持续的以离子液体为基础的分子平台,用于设计乙胆酶活性剂
Illia V Kapitanov1, Marcel Špulák2, Milan Pour2
1Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia Tee 15, 12618 Tallinn, Estonia.
Chemico-biological interactions
|October 6, 2023
概括
新的氧化物功能化的离子液体 (IL) 被合成为乙胆酶 (AChE) 反激活剂. 一种化合物与标准治疗相比,对VX抑制的ACHE具有更高的疗效,具有较低的毒性.
科学领域:
- 绿色化学是一种绿色化学.
- 药品化学 药品化学 是一个
- 生物化学 生物化学
背景情况:
- 器官酸盐 (OP) 中毒仍然是一个重大威胁,需要有效的乙胆酶 (AChE) 反激活剂.
- 目前的再激活剂具有局限性,这推动了对新型治疗剂的研究.
- 离子液体 (ILs) 为药物开发提供可调节的特性.
研究的目的:
- 开发新的氧化物功能化的ILs作为潜在的ACHE活性化剂.
- 评估这些合成化合物的疗效和安全性.
- 为了研究改善抗毒性质的结构-活性关系.
主要方法:
- 绿色化学合成胺/ ester 连接的 ILs 与基多キシ部分.
- 在体外评估对沙林 (GB),VX和偏氧子 (PON) 抑制酶的ACHE活性.
- 对细菌,真菌和真核细胞系的细胞毒性测定 (CHO-K1).
- 生物降解性和血稳定性的评估.
- 分子对接研究. 分子对接研究.
主要成果:
- 合成了具有不同链接类型 (胺基/) 和氨基酸衍生物 (l-alanine,l-phenylalanine) 的新型氧化物功能化IL.
- 化合物显示出显著的ACHE活性,其中化合物3d对VX抑制的ACHE表现出显著的活性,超过2-PAM和obidoxime.
- 大多数化合物在经过测试的微生物和真核细胞系中显示出低毒性,直至2mM.
- 引入氧化物部分降低了母结构的生物降解性.
- 分子对接为结合相互作用提供了洞察力.
结论:
- 氧化物功能化的ILs是具有良好的安全概况的有希望的ACHE活性剂类别.
- 化合物3d显示出作为下一代对OP中毒的解药的潜力,特别是对VX.
- 根据观察到的规律性进行进一步的结构修改,预计将增强抗毒剂活性,稳定性和生物降解性.
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