[O,O-dialkyl-S-bromomethylthiophosphates–inhibitors of mammalian choline- and carboxyl esterases: structure-activity relationship].

The research investigates the interaction dynamics between certain potential pesticide compounds and three types of esterases found in warm-blooded animals, with the aim to understand their inhibitory effects and the relationship between the structures of these substances and their inhibitory activities.

Investigation of Inhibitory Effects

• The study focuses on the compounds O,O-dialkyl S-bromomethylthiophosphates (RO)2P(O) SCH2Br. These compounds are potential pesticides and are examined for their ability to inhibit esterases, which are a type of enzyme found in warm-blooded animals.
• The three esterases investigated are acetylcholinesterase, butyryl cholinesterase, and carboxyl esterase.
• The research found that all the compounds under study irreversibly inhibited these esterases, and also establishes their rates of inhibition.
• Among the three esterases, the most sensitive to inhibition was found to be the carboxyl esterase.

Exploration of Structure-Activity Relationship

• The research applied the Hansch and Kubinyi technique of multiple regression analysis to analyze the relationship between the structure of the studied compounds and their ability to inhibit acetylcholinesterase and butyryl cholinesterase.
• The results show that hydrophobic interactions are important for the inhibition of both enzymes, but their effect is more significant in the case of butyryl cholinesterase.
• In contrast, steric factors, which involve the spatial arrangement of atoms in a molecule, are especially significant in the inhibition of acetylcholinesterase.
• For both enzymes, it was found that steric hindrances, or obstacles to the interaction caused by the three-dimensional structure of the molecules, influence the phosphorylation stage of the enzyme where a phosphate group is added to the enzyme, altering its function.