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羟基吡啶酮衍生物:一类具有治疗应用的迷人螯合剂——最新进展

Hydroxypyridinone Derivatives: A Fascinating Class of Chelators with Therapeutic Applications - An Update.

作者信息

Chaves Sílvia, Piemontese Luca, Hiremathad Asha, Santos Maria A

机构信息

Centro de Quimica Estrutural, Instituto Superior Tecnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa. Portugal.

出版信息

Curr Med Chem. 2018;25(1):97-112. doi: 10.2174/0929867324666170330092304.

Abstract

Hydroxypyridinones (HPs) are a family of N-heterocyclic metal chelators, which have been an attractive target in the development of a variety of new pharmaceutical drugs, due to their high metal chelating efficacy/specificity and easy derivatization to tune the desired biological properties. In fact, along the last decades, hydroxypyridinone derivatives, but mostly 3-hydroxy-4-pyridinone (3,4-HP), have been intensively used in drug design, following either a multitarget approach, in which one chelating unity is extrafunctionalized (hybridized) to enable the interaction with other important specific biological sites, or a polydenticity approach, in which more than one chelating moiety is conveniently attached to one scaffold, to increase the metal chelating efficacy. This review represents an update of the most recent publications (2014-2016) in mono-HP hybrids, namely as potential anti-Alzheimer's drugs, inhibitors of metalloenzymes and anti-microbials, and also polychelating compounds (poly- HP), in view of potential application, such as anti-microbial/biostatic agents, luminescent biosensors or diagnostic agents.

摘要

羟基吡啶酮(HPs)是一类N-杂环金属螯合剂,由于其具有高金属螯合效力/特异性以及易于衍生化以调节所需生物学特性,在多种新型药物的开发中一直是一个有吸引力的目标。事实上,在过去几十年中,羟基吡啶酮衍生物,尤其是3-羟基-4-吡啶酮(3,4-HP),已被广泛应用于药物设计,采用多靶点方法,即一个螯合单元进行额外功能化(杂化)以实现与其他重要特定生物位点的相互作用,或者采用多齿方法,即一个以上的螯合部分方便地连接到一个支架上,以提高金属螯合效力。本综述介绍了单-HP杂化物(即作为潜在的抗阿尔茨海默病药物、金属酶抑制剂和抗菌剂)以及多螯合化合物(聚-HP)的最新出版物(2014 - 2016年)的更新情况,考虑到其潜在应用,如抗微生物/抑菌剂、发光生物传感器或诊断剂。

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