Supramolecular hosts as in vivo sequestration agents for pharmaceuticals and toxins.
Supramolecular hosts as in vivo sequestration agents for pharmaceuticals and toxins.
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DOI：
10.1039/d0cs00454e
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发表时间：
2020-11-07
影响因子：
46.2
通讯作者：
Isaacs LD
中科院分区：
文献类型：
--
作者：
Deng CL ;Murkli SL ;Isaacs LD
药剂、滥用药物和有毒物质对现代社会产生了积极和消极的巨大影响。减轻药物副作用和抵消药物滥用和毒素对生命的威胁可以通过基于生物受体•药物拮抗的药效学（PD）方法或通过寻求降低游离药物浓度的药代动力学（PK）方法来实现。在本教程综述中，我们介绍了超分子宿主（环dextrins， calixarenes,（无环）瓜脲和柱芳烃）作为体内隔离剂的使用，通过PK方法来隔离神经肌肉阻滞剂，滥用药物（甲基苯丙胺和芬太尼），麻醉剂，神经毒素，农药百草枯和肝素抗凝剂。综述了超分子寄主的基本物理和分子识别特征，以及在体内隔离应用中选择和结构优化的一些原则。还提到了主客体络合对药物的其他相关体内特性（如分布、循环时间、排泄、氧化还原特性）的影响。文章最后讨论了未来的发展方向。
Pharmaceutical agents, drugs of abuse, and toxic substances have a large impact, positive and negative, on modern society. Efforts to mitigate the side effects of pharmaceuticals and counteract the life threatening effects of drugs of abuse and toxins can occur either by pharmacodynamic (PD) approaches based on bioreceptor•drug antagonism or by pharmacokinetic (PK) approaches that seek to reduce the concentration of free drug. In this tutorial review, we present the use of supramolecular hosts (cyclodextrins, calixarenes, (acyclic) cucurbiturils, and pillararenes) as in vivo sequestration agents for neuromuscular blockers, drugs of abuse (methamphetamine and fentanyl), anesthetics, neurotoxins, the pesticide paraquat, and heparin anti-coagulants by the PK approach. The review presents the basic physical and molecular recognition features of the supramolecular hosts and some of the principles used in their selection and structural optimization for in vivo sequestration applications. The influence of host•guest complexation on other relevant in vivo properties of drugs (e.g. distribution, circulation time, excretion, redox properties) are also mentioned. The article concludes with a discussion of future directions.
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