Synthesis and in vitro screening of N-phenacylpyridinium oximes as reactivators of organophosphorus (OP)-inhibited electric eel acetylcholinesterase (AChE)

Autor:	Aditya Kapil Valiveti, Jyotiranjan Acharya, Anand K. Halve, Mahabir Parshad Kaushik, Ajay Pratap
Rok vydání:	2015
Předmět:	Obidoxime Sarin biology Stereochemistry Organic Chemistry Oxime biology.organism_classification Phenacyl Medicinal chemistry Acetylcholinesterase Electric eel chemistry.chemical_compound chemistry medicine Pyridinium General Pharmacology Toxicology and Pharmaceutics medicine.drug Nerve agent
Zdroj:	Medicinal Chemistry Research. 24:3353-3371
ISSN:	1554-8120 1054-2523
DOI:	10.1007/s00044-015-1384-y
Popis:	Pyridinium oxime-based drugs are generally used in the treatment of acute organophosphorus (OP) nerve agent poisoning. In this regard, a series of mono-pyridinium oximes bearing substituted phenacyl moieties as side chain were synthesized and screened for their in vitro reactivation efficacies against electric eel acetylcholinesterase (AChE) inhibited by OP inhibitors such as DFP, sarin and VX. The results of the in vitro reactivation data of the synthesized compounds were compared to standard antidotes 2-PAM and obidoxime. Among the synthesized compounds, 1a, 2a, 7a, 8a, 11a, 12a, 13a, 14a and 16a have shown better reactivation efficacy than 2-PAM and obidoxime against VX-inhibited AChE. Oximes 8a, 8b, 11a and 12a were at par with obidoxime in the reactivation of sarin-inhibited AChE. The pKa values for all the oximes were determined and correlated with their observed reactivation potential.
Databáze:	OpenAIRE
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