主客体化学应用于药物拮抗剂设计研究  

Host-guest chemistry for the design of drug antagonists

作　　者：余尚博 周伟[2] 田佳 马达 张丹维[2] 黎占亭[1,2] Shang-Bo Yu;Wei Zhou;Jia Tian;Da Ma;Dan-Wei Zhang;Zhan-Ting Li(Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China;Department of Chemistry,Fudan University,Shanghai 200438,China;School of Pharmaceutical Engineering and Institute for Advanced Studies,Taizhou University,Taizhou 318000,China)

机构地区：[1]中国科学院有机功能分子合成与组装化学重点实验室,中国科学院上海有机化学研究所,上海200032 [2]复旦大学化学系,上海200438 [3]台州学院医药化工学院,台州318000

出　　处：《中国科学：化学》2023年第12期2345-2356,共12页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:22271059,21921003,21890730,21890732)资助项目。

摘　　要：很多药物在体内残留导致毒副作用.基于残留药物在血液内循环的特征,设计分子、大分子和超分子主体,利用主客体化学原理络合和捕集血液内的残留药物,降低其游离浓度,加速其通过肾脏排泄,实现拮抗和消除这些残留药物毒副作用的目的,是近年来主客体化学研究的重要方向,也是功能超分子体系研究的重要应用出口.本文总结了近年来利用环糊精、杯芳烃、柱芳烃及其类似物、葫芦脲和开环葫芦脲、超分子有机框架和柔性有机框等设计残留药物拮抗剂方面取得的进展,讨论了针对残留药物开展主客体化学的一般原则和识别特征,最后提出了推进针对药物拮抗的主客体体系进一步走向临床前研究需要考虑和解决的挑战.Many drugs remain as residuals in the body after exhibiting therapeutic function,causing various toxicities or side effects that may lead to the death of the patients.By making use of host-guest complexation principle,in the past decade supramolecular chemists have devoted great effort to the design of molecular,macromolecular and supramolecular substrates for binding and sequestrating drug residuals in the blood,aiming to reduce their free concentration in the blood,promote their renal excretion and eventually inhibit their toxicity.This effort also represents one of the most important routes for the development of the functions of host-guest systems.This review summarizes the recent progresses in the applications of cyclodextrins,calixarenes,pillararenes and analogues,(acyclic)cucurbit[n]urils,supramolecular organic frameworks as well as flexible organic frameworks for the development of antagonists for neuromuscular blocking agents,anticoagulants and photodynamic agents.We discuss the general principles and features for host structures and driving forces that allow for the achievement of efficient binding of the drugs and finally provide our opinions for challenges that need to be addressed in the future for further preclinical studies.

关 键 词：主客体化学 药物残留 拮抗 大环化合物 多孔聚合物 分子识别 

分 类 号：TQ460.1[化学工程—制药化工]