title: New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase.
abstract: Herein, we described a new class of uncharged non-pyridinium reactivators for nerve agent-inhibited acetylcholinesterase (AChE). Based on a dual site binding strategy, we conjugated the imidazolium aldoxime to different peripheral site ligands (PSLs) of AChE through alkyl chains. Compared with the known quaternary pyridinium reactivators, two of the resulting conjugates (7g and 7h) were highlighted to be the first efficient non-pyridinium oxime conjugates exhibiting similar or superior ability to reactivate sarin-, VX- and tabun-inhibited AChE. Moreover, they were more broad-spectrum reactivators.
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Military Toxicology and Biochemical Pharmacology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Xin-Bo
authors.initials: XB
authors.lastname: Zhou
authors.affiliation: Department of Military Toxicology and Biochemical Pharmacology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Military Toxicology and Biochemical Pharmacology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Chun-Qian
authors.initials: CQ
authors.lastname: Huang
authors.affiliation: Department of Military Toxicology and Biochemical Pharmacology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Wang
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: zzbcaptain@aliyun.com.
authors.forename: Zhi-Bing
authors.initials: ZB
authors.lastname: Zheng
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002619:Chemical Warfare Agents / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D007093:Imidazoles; D008024:Ligands; D010091:Oximes; C029899:imidazole; D000110:Acetylcholinesterase; C023728:acetaldehyde oxime
keywords: Human acetylcholinesterase; Imidazolium aldoxime; Nerve agent; Peripheral site ligand; Reactivator