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Paper Information

Journal:   KOWSAR MEDICAL JOURNAL   Spring 2002 , Volume 7 , Number part 1; Page(s) 21 To 26.
 
Paper: 

QUANTITATIVE-STRUCTURE ACTIVITY RELATIONSHIP (QSAR) OF OXIMES IN REACTIVATION OF ACETYLCHOLINESTERASE INHIBITED BY NERVE AGENTS

 
 
Author(s):  TAHANEJAD F.S.*
 
* Faculty of Medicine, Baghiyatallah(a.s.) University of Medical sciences, Tehran, IR of IRA
 
Abstract: 
Quantitative Structure Activity Relationship(QSAR) methods are used for correlation between biological activity and physicochemical parameteres of compounds.
Organophosphates known as chemical warfare agents are extremely potent inhibitors of acetylcholinesterase. Oximes with reactivation of the enzyme cholinesterase are very important in treatment of war victims. None of standard oximes penetrate the blood-brain barrier readily, nor are the effective against aged enzyme. New generation of oximes (H-series) have greater activity than the conventional oximes, particularly against soman. However, their instability in aqueous solution and lack of effectiveness against tabun poisoning mandate of further efforts in developing new oximes. Hansch linear multiple regression analysis was applied on bisquaternary oxime compounds to determine their structural requirements necessary for binding. Quantitative structure activity relationship in two groups of oximes containing trimethylene or ether bridges in their structures were studied by means of computerized method of analysis. Biological activity of the parent molecule in a series of compounds was analyzed and related equations for each analysis were gained. These equations show the correlation between biological activity and physicochemical parameteres (electronic, hydrophobic and steric factors) in each group of compounds which were studied. According to the results, electronic and hydrophobic effects have significant relation with biological activity of oximes in cholinesterase reactivation.
In oximes containing trimethylene bridges between two pyridinium rings, placing an electron withdrawing group at para position of the pyridinium ring will increase activity, while hydrophobic parameter shows negative correlation with biological activity.
As a conclusion, the whole activity of the oximes studied depend on the position of the oxime group in one of the pyridinium rings and the type and/or position of another non-oxime group in another pyridinium ring.
 
Keyword(s): QSAR, OXIMES, ORGANOPHOSPHATES, ACETYLCHOLINESTERASE
 
References: 
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  Persian Abstract Yearly Visit 56
 
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