[Inhibition of cholinesterases by aziridinium derivatives of polymethylene bischloroethylamines].
Cyclization of polymethylene bischloroethylamines, differing in the methylene chain-length (n = 6 or 10) and the N-substituents (R = CH3 or CH2C6H5), was carried out and the respective aziridinium derivatives were obtained. These derivatives of hexamethonium and decamethonium manifested reversible inhibition (Ki approximately 100-1 microM) and irreversible alkylating activity (kII approximately 10(2) M-1 . min-1) towards acetylcholinesterase from human erythrocytes and horse serum butyrylcholinesterase. Upon varying n and R, the alkylation biomolecular rate constants changed symbately with changes in the reversible inhibition constants. The most potent alkylating agent with respect to acetylcholinesterase (kII 7,8 x 10(2) M-1 . min-1) and butyrylcholinesterase (kII 4,2 . 10(2) M-1 . min-1) was found to be the aziridinium analog of hexamethonium with R = CH2C6H5. Based on the kinetic data, the problem of alkylation of anionic sites in the catalytic and allosteric centers of the two cholinesterases is discussed.
D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood*; D003650:Decamethonium Compounds / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006736:Horses; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D011095:Polyethylenes / Q000494:pharmacology*; D013379:Substrate Specificity
D001388:Aziridines; D001389:Azirines; D002800:Cholinesterase Inhibitors; D003650:Decamethonium Compounds; D006584:Hexamethonium Compounds; D011095:Polyethylenes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases
Ingibirovanie kholinésteraz aziridinievymi proizvodnymi polimetilenbiskhlorétilaminov.