Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice

被引：4

作者：

Wei, Zhao ^{[1
]}

Zhang, Xinlei ^{[1
]}

Nie, Huifang ^{[1
]}

Yao, Lin ^{[1
]}

Liu, Yanqin ^{[2
]}

Zheng, Zhibing ^{[2
]}

Ouyang, Qin ^{[3
]}

机构：

[1] Air Force Med Univ, Sch Pharm, Dept Med Chem, Xian 300071, Peoples R China

[2] Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

[3] Third Mil Med Univ, Sch Pharm, Dept Med Chem, Chongqing 400038, Peoples R China

来源：

MOLECULES | 2022年 / 27卷 / 03期

基金：

中国国家自然科学基金;

关键词：

organophosphate; acetylcholinesterase; non-oximes; reactivators; Mannich phenol; NONQUATERNARY REACTIVATORS; UNCHARGED REACTIVATORS; PYRIDINIUM OXIMES; ORGANOPHOSPHORUS; ACETYLCHOLINESTERASE; DESIGN; SOMAN; PROTECTION; ALDOXIME;

D O I：

10.3390/molecules27031096

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD50 sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency.

引用

页数：13

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