title: Inhibition of human plasma cholinesterase by malachite green and related triarylmethane dyes: mechanistic implications.
abstract: The inhibitory effects of the cationic triarylmethane (TAM+) dyes, pararosaniline (PR+), malachite green (MG+), and methyl green (MeG+) on human plasma cholinesterase (BChE) were studied at 25 degrees C in 100 mM Mops, pH 8.0, with butyrylthiocholine as substrate. PR+ and MG+ caused linear mixed inhibition of enzyme activity. The respective inhibitory parameters were K(i) = 1.9 +/- 0.23 microM, alpha = 13 +/- 48, beta = 0 and K(i) = 0.28 +/- 0.037 microM, alpha = 23 +/- 7.4, beta = 0. MeG+ acted as a competitive inhibitor with K(i) = 0.12 +/- 0.017 microM (alpha, infinity, beta, not applicable). The K(i) values were within the same range reported for a number of ChE inhibitors including propidium ion, donepezil, and the phenothiazines, suggesting that TAM+s are active site ligands. On the other hand, the alpha values failed to correlate with values previously reported for a number of ChE inhibitors. It appears that mixed inhibition is the combined result of more than one type of binding and S-I interference. The impact of ligands at the choline-specific and peripheral anionic sites (or, possibly, accessory structural domains) on BChE activity needs to be studied in further detail.
authors.affiliation: Department of Biochemistry, School of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
authors.forename: Tuba
authors.initials: T
authors.lastname: Küçükkilinç
authors.forename: Inci
authors.initials: I
authors.lastname: Ozer
mesh_terms: D001665:Binding Sites; D002092:Butyrylthiocholine / Q000737:chemistry / Q000378:metabolism*; D002794:Choline / Q000097:blood / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D000077265:Donepezil; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007189:Indans / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008739:Methyl Green / Q000737:chemistry / Q000494:pharmacology; D010525:Peripheral Nerves / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011419:Propidium / Q000494:pharmacology; D012394:Rosaniline Dyes / Q000737:chemistry / Q000494:pharmacology*; D013696:Temperature; D014052:Toluidines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D008024:Ligands; D010640:Phenothiazines; D010880:Piperidines; D012394:Rosaniline Dyes; D014052:Toluidines; C005095:malachite green; C005409:pararosaniline; D011419:Propidium; D002092:Butyrylthiocholine; D008739:Methyl Green; D000077265:Donepezil; D002802:Cholinesterases; D002794:Choline