Department of Chemistry, Federal University of Lavras, Lavras 37200-000, Brazil.
Department of Chemistry, Faculty of Science, University of Hradec Kralove, 500 03 Hradec Kralove, Czech Republic.
Biomolecules. 2020 Mar 12;10(3):436. doi: 10.3390/biom10030436.
Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall under the cholinergic syndrome spectra. To combat the toxic effects of some AChEI, such as organophosphorus (OP) nerve agents, many compounds with reactivator effects have been developed. Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. This review was developed with the purpose of covering the new advances in AChE reactivation. Over the past years, researchers worldwide have made efforts to identify and develop novel active molecules. These researches have been moving farther into the search for novel agents that possess better effectiveness of reactivation and broad-spectrum reactivation against diverse OP agents. In addition, the discovery of ways to restore AChE in the aged form is also of great importance. This review will allow us to evaluate the major advances made in the discovery of new acetylcholinesterase reactivators by reviewing all patents published between 2016 and 2019. This is an important step in continuing this remarkable research so that new studies can begin.
乙酰胆碱酯酶(AChE)是负责使 ACh 神经递质失活的关键酶。因此,AChE 的不可逆或长期抑制会导致突触 ACh 升高,从而导致严重的中枢和外周不良影响,这些影响属于胆碱能综合征谱。为了对抗某些 AChEI(如有机磷(OP)神经毒剂)的毒性作用,已经开发了许多具有重活化作用的化合物。在最突出的重活化剂中,肟类物质引人注目,它们在重活化 AChE 和恢复正常突触乙酰胆碱(ACh)水平方面表现出良好的性能。本综述旨在涵盖 AChE 重活化的新进展。在过去的几年中,世界各地的研究人员都在努力识别和开发新型活性分子。这些研究已经进一步深入到寻找具有更好重活化效果和广谱重活化针对各种 OP 制剂的新型试剂。此外,发现恢复 AChE 老年形式的方法也非常重要。通过审查 2016 年至 2019 年期间公布的所有专利,我们将能够评估在发现新型乙酰胆碱酯酶重活化剂方面取得的主要进展。这是继续这项卓越研究的重要一步,以便新的研究能够开始。