Silicon Containing Organophosphorus Compounds with Anticholinesterase Activity

6 Silicon Containing Organophosphorus Compounds with Anticholinesterase Activity 

The toxicity of organophosphoric esters for insects and mammals is associated with inhibition of cholinesterases. Investigations on the relation between chemical structure of organophosphoric esters and the inactivation of acetylcholinesterase (AChE) have revealed that anticholinesterase activity depends to a large extent on the chemical reactivity of the esters. As a rule, the chemical reactivity of the phosphorus atom is the single most important property which determines the anticholinesterase activity of an organophosphoric ester. 

Organophosphates phosphorylate AChE by virtue of an electrophilic attack of the P atom on a serine hydroxyl of AChE, as shown in Eq. (21) for paraoxon (106)  

107a ED50 = 1044 (442.6-2466.4) mmol/1 human serum 107b EDS0 = 158.1 (58.8-424.8) mmol/1 human serum 

The silicon compound 107b acts 6.6 times more strongly than its carbon analogue 107a. Paraoxon was found to be more active than the silicon compound 107b [106 EDso = 20.7 (7.7—55.4) mmol/1 human serum]. Further investigations are in progress. 

---