Development of quantitative structure activity relationships for the binding affinity of methoxypyridinium cations for human acetylcholinesterase.
Among the most toxic substances known are the organophosphorus (OP) compounds used as pesticides and chemical warfare agents. Owing to their high toxicity there is a number of efforts underway to develop effective therapies for OP agent exposure. To date all therapies in use treat inhibited acetylcholinesterase (AChE), but are ineffective for the treatment of inhibited AChE, which has undergone a subsequent hydrolysis process, referred to as aging. Toward developing a therapy for treating victims of OP intoxication in the aged state we have developed Quantitative Structure-Activity Relationships (QSARs) based on the AM1 semiempirical quantum mechanical method using the program, CODESSA (COmprehensive Descriptors for Structural and Statistical Analysis). Using this methodology we obtained a multiple correlation QSAR equation which gave R(2)=0.9359 for a random training set of 38 ligands and R(2)=0.9236 for prediction on a random test set of 9 ligands.
['Morrill|Jason A|JA|', 'Topczewski|Joseph J|JJ|', 'Lodge|Alexander M|AM|', 'Yasapala|Nilanthi|N|', 'Quinn|Daniel M|DM|']
D000110:Acetylcholinesterase D020134:Catalytic Domain D002800:Cholinesterase Inhibitors D002801:Cholinesterase Reactivators D006801:Humans D062105:Molecular Docking Simulation D010755:Organophosphates D025341:Principal Component Analysis D011485:Protein Binding D011726:Pyridinium Compounds D021281:Quantitative Structure-Activity Relationship
Methoxypyridinium cations QSAR AM1 AChE binding affinity