Interaction of hexafluorenium with human plasma cholinesterase in comparison with hexamethonium.
1. The influence of the 2 alkane-bis-onium compounds hexafluorenium (HF1) and hexamethonium (C6) on human plasma cholinesterase (ChE) was studied with respect to the type of inhibition. 2. HF1 and C6 are reversible inhibitors of ChE. The inhibitory potency of HF1 (pI50 = 6.96; Ki = 2.4 x 10(-9)) is about 40 000-fold higher than that of C6 (pI50 = 2.4; Ki = 6.7 x 10(-2)). 3. The kinetic analysis displayed a competitive (C6) and a non-competitive (hf1) mechanism of action. 4. The inhibition of ChE by C6 is induced by a binding of C6 to the anionic site of the active center thus impairing the primary formation of the enzyme-substrate complex. HF1, however, is most probably bound to anionic side receptors in the vicinity of the active center; by that a conformational change of the enzyme protein is induced impairing the acylation step of the esteratic site.
D001665:Binding Sites; D001667:Binding, Competitive; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000097:blood*; D005449:Fluorenes / Q000494:pharmacology*; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009994:Osmolar Concentration; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D005449:Fluorenes; D006584:Hexamethonium Compounds; C005034:hexafluorenium; D002802:Cholinesterases