Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review

被引:49
|
作者
Sharma, Rahul [1 ]
Gupta, Bhanushree [1 ]
Singh, Namrata [1 ,2 ]
Acharya, J. R. [3 ]
Musilek, Kamil [4 ,5 ]
Kuca, Kamil [4 ,5 ]
Ghosh, Kallol Kumar [1 ]
机构
[1] Pt Ravishankar Shukla Univ, Sch Studies Chem, Raipur 492010, CG, India
[2] Charles Univ Prague, Fac Med 1, Dept Psychiat, Prague 12000 2, Czech Republic
[3] Def Res & Dev Estab, Proc Technol Dev Div, Gwalior 474002, MP, India
[4] Univ Hradec Kralove, Fac Sci, Dept Chem, Hradec Kralove 50003, Czech Republic
[5] Univ Hosp, Biomed Res Ctr, Hradec Kralove 50005, Czech Republic
关键词
AChE; BBB; chemical warfare agents; organophosphates; oxime; reactivator; IN-VITRO REACTIVATION; BIS-PYRIDINIUM OXIMES; BLOOD-BRAIN-BARRIER; ELECTRIC-EEL ACETYLCHOLINESTERASE; BISPYRIDINIUM COMPOUNDS BEARING; EFFICIENT UNCHARGED REACTIVATORS; TOXIC ORGANOPHOSPHORUS COMPOUNDS; NERVE AGENTS; THERAPEUTIC-EFFICACY; CRYSTAL-STRUCTURES;
D O I
10.2174/1389557514666141128102837
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.
引用
收藏
页码:58 / 72
页数:15
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