Title : [O,O-dialkyl-S-bromomethylthiophosphates--inhibitors of mammalian choline- and carboxyl esterases: structure-activity relationship] - Makhaeva_1999_Bioorg.Khim_25_3 |
Author(s) : Makhaeva GF , Iankovskaia VL , Kovaleva NV , Fetisov VI , Malygin VV , Torgasheva NA , Khaskin BA |
Ref : Bioorganicheskaia Khimiia , 25 :3 , 1999 |
Abstract :
The interaction kinetics of potential pesticides, O,O-dialkyl S-bromomethylthiophosphates (RO)2P(O) SCH2Br (R = Et, i-Pr, n-Pr, n-Bu, or n-Am) with acetylcholinesterase, butyryl cholinesterase, and carboxyl esterase from warm-blooded animals was studied. All the compounds irreversibly inhibit these esterases, with k1 (M-1 min-1) being 1.8 x 10(4) - 1.9 x 10(6) for acetylcholinesterase, 2.0 x 10(6) - 4.1 x 10(7) for the more sensitive butyryl cholinesterase, and 2.3 x 10(7) - 2.3 x 10(8) and higher for the most sensitive carboxyl esterase. By using the Hansch and Kubinyi technique of multiple regression analysis, we quantitatively analyzed the relationship between the structure and inhibiting activity of these substances toward acetylcholinesterase and butyryl cholinesterase. Hydrophobic interactions were found to be important for the inhibition of both enzymes but are more pronounced in the case of butyryl cholinesterase. On the other hand, steric factors were much more significant in the inhibition of acetylcholinesterase. For both enzymes, the steric hindrances affect the phosphorylation stage of the enzyme. |
PubMedSearch : Makhaeva_1999_Bioorg.Khim_25_3 |
PubMedID: 10234439 |
Makhaeva GF, Iankovskaia VL, Kovaleva NV, Fetisov VI, Malygin VV, Torgasheva NA, Khaskin BA (1999)
[O,O-dialkyl-S-bromomethylthiophosphates--inhibitors of mammalian choline- and carboxyl esterases: structure-activity relationship]
Bioorganicheskaia Khimiia
25 :3
Makhaeva GF, Iankovskaia VL, Kovaleva NV, Fetisov VI, Malygin VV, Torgasheva NA, Khaskin BA (1999)
Bioorganicheskaia Khimiia
25 :3