ABSTRACT
To study the influence of onium atom nature on anticholinesterase efficiency of elementorganic derivatives of tetramethylenbisonium compounds as reversible inhibitors of cholinesterase (ChE) - acetyl-ChE from human erythrocytes, butyryl-ChE from horse serum, ChE from the brain of frog Rana temporaria and ChEs from visual ganglia of Pacific squid Todarodes pacificus and individuals of Comman- der squid Berryteuthis magister from different habitats in the northwestern Pacific Ocean were investigated. Bisphosphonium inhibitors were significantly more potent effectors than bisammonium ones, but this may be associated with a significantly increased size and hydrophobicity of onium groups of the former. Bisammonium organosilicon compound and its monoammonium analogue were equally active reversible ChE inhibitors in mammals. First studied bis(phenyliodonium) derivative, which is characterized by a significant increase in the degree of hydrophobicity due to introduction of fluorine atoms in the interonium tetramethylene chain, also had marked anticholinesterase effects on mammalian ChE.
Subject(s)
Acetylcholinesterase/chemistry , Butyrylcholinesterase/chemistry , Cholinesterase Inhibitors/chemistry , Onium Compounds/chemistry , Animals , Decapodiformes , GPI-Linked Proteins/antagonists & inhibitors , GPI-Linked Proteins/chemistry , Horses , Humans , Rana temporariaABSTRACT
The review presents data on comparative reactivity of 68 cholinesterase preparation from various organs and tissues in a number of vertebrates and invertebrates based on sensitivity to two highly specific and most studied organophosphorus inhibitors--diisopropyl fluorophosphates (DFP) and (2-ethoxymethyl phosphoryl thioethyl) ethyl (methyl) sulphonium sulphomethylat (GD-42). Analysis of these data suggests a great diversity in enzymologic characteristics of cholinesterase preparation in representatives of vertebrates and invertebrates, this variety observed even for closely related enzymes in animals of almost the same level of development.
Subject(s)
Cholinesterase Inhibitors/chemistry , Cholinesterases/chemistry , Isoflurophate/chemistry , Organothiophosphorus Compounds/chemistry , Animals , Humans , Species SpecificityABSTRACT
To check whether the horse blood serum butyrylcholinesterase expresses transferase activity at the complex ester hydrolysis in the presense of several low-molecular aliphatic alcohols, a study was performed with aid of the chromogenic substrate 1-methyl-8-acetoxychinolium whose phenolic hydrolysis product absorbs intensively at 445 nm, whereas the initial ester in this specter area practically does not absorb. This allowed measuring simultaneously the products of accumulation of both products of enzymatic hydrolysis: of acetic acid by the potentiometric, while of phenol--by the photometric method. Rates of formation of both products of enzymatic hydrolysis are practically equal in experiments with all studied alcohols. This indicates that horse blood serum butyrylcholinesterase under these experimental conditions does not catalize transfer of acetyl residue to the studied aliphatic alcohols, i. e. does not have transefase activity.
Subject(s)
Blood Proteins/chemistry , Butyrylcholinesterase/chemistry , Quinolinium Compounds/chemistry , Spectrophotometry/methods , Alcohols/chemistry , Animals , Butyrylcholinesterase/blood , Chromogenic Compounds/chemistry , Horses , Hydrolysis , Spectrophotometry/instrumentationABSTRACT
Specifically synthesized group of benzimidazole derivatives possessing varying degrees of delocalization of the positive charge in the cation group of the molecule has been studied in order to search for potential cholinergically active compounds and to study the role of the Coulomb interaction in cholinesterase catalysis. These compounds were reversible inhibitors of cholinesterase (ChE) of human erythrocytes, horse serum, brain of the frog Rana temporaria and visual ganglia of the Pacific squid Todarodes pacificus in the presence of acetylthiocholine iodide and propionylthiocholine iodide as substrates. The differences in the nature of reversible inhibitory effect were observed. The effect of the inhibitor structure and substrate nature, specific for each of the studied inhibitors, on the character of the process of reversible inhibition was found.
Subject(s)
Benzimidazoles/pharmacology , Cholinesterase Inhibitors/pharmacology , Cholinesterases/chemistry , Acetylthiocholine/analogs & derivatives , Acetylthiocholine/chemistry , Animals , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Brain Chemistry , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Cholinesterases/isolation & purification , Decapodiformes , Erythrocytes/chemistry , Erythrocytes/enzymology , Ganglia, Sensory/chemistry , Ganglia, Sensory/enzymology , Horses , Humans , Kinetics , Rana temporaria , Static Electricity , Structure-Activity Relationship , Substrate Specificity , Thiocholine/analogs & derivatives , Thiocholine/chemistryABSTRACT
The paper is a review of literature data on interaction of the mammalian erythrocyte acetylcholinesterase and blood serum butyrylcholinesterase with a group of isomer complex ester derivatives (acetates, propionates, butyrates, valerates, and isobutyrates) of bases and iodomethylates of ephedrine and its enantiomer pseudoephedrine. For 20 alkaloid monoesters, parameters of enzymatic hydrolysis are determined and their certain specificity toward acetylcholinesterase is revealed, whereas 5 diesters of iodomethylates of pseudoephedrine were hydrolyzed only by butyrylcholinesterase. The studied 20 aklaloid diesters and 10 trimethylammonium derivatives turned out to be non-competitive reversible inhibitors of acetylcholinesterase and competitive inhibitors of butyrylcholinesterase. The performed for the first time isomer and enantiomer analysis "structure-efficiency" has shown that in most cases it is possible to state the greater comlementarity of the catalytical surface of enzymes for ligands of the pseudoephedrine structure, such differentiation being realized more often at the reversible inhibition of enzymes. pseudoephedrine.
Subject(s)
Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Ephedrine/analogs & derivatives , Pseudoephedrine/analogs & derivatives , Animals , Cholinesterase Inhibitors/chemistry , Ephedrine/chemistry , Ephedrine/pharmacology , Humans , Ligands , Protein Binding , Pseudoephedrine/chemistry , Pseudoephedrine/pharmacologyABSTRACT
There was studied action of aliphatic alcohols (ethanol, propanol, isopropanol, n-butanol, isobutanol, secbutanol, tretbetanol) and pH on various kinds of reactional capability the serum cholinesterase. At the alcohols-affected inhibition of the cholinesterase hydrolytic activity, the determining role was played not the total number carbon atoms in the alcohol molecule, but by the "effective length" of the carbohydrate chain. The fact that the presence of alcohols did not affect parameters of the reverse cholinesterase inhibition with onium ions tetramethylammonium and choline allows suggesting the absence of effect solvents on specific acetylcholine sorption in the enzyme active center. With aid of two rows of hydrophobic organophosphorus inhibitors (OPI), we have managed to estimate both the degree and the character itself of the modifying action of alcohols and pH on the process of irreversible inhibition of serum cholinesterase.
Subject(s)
Alcohols/chemistry , Cholinesterase Inhibitors/chemistry , Cholinesterases/chemistry , Organophosphorus Compounds/chemistry , Alcohols/blood , Animals , Catalytic Domain , Horses , Hydrogen-Ion ConcentrationABSTRACT
Arylsulfoesters and carbonic lupinin esters are studied for the first time as reversible inhibitors of mammalian blood cholinesterases. Studied in detail is sensitivity of cholinesterases to mono- and bislupinin inhibitors in Commander squid individuals from different habitation zones.
Subject(s)
Acetylcholinesterase/blood , Butyrylcholinesterase/blood , Cholinesterase Inhibitors , Decapodiformes/enzymology , Sparteine/analogs & derivatives , Anabasine/chemistry , Animals , Cholinesterase Inhibitors/chemistry , Eye/enzymology , Eye/innervation , Ganglia/enzymology , Horses , Humans , Sparteine/chemistry , Species SpecificityABSTRACT
The isomeric-structure analysis data of anticholinesterase action of organophosphorous inhibitors with similar structure help in the search of specific effectors and detection of differences in reactivity of various animals' enzymes. This study compared the data of efficacy in respect of 4 mammal and 5 arthropoda cholinesterase preparations for 26 quinolizidine inhibitors, which molecules contain both the isomeric unbranched and branched alkoxyl radicals in the phosphoryl group, and the epimeric lupinine and epilupinine derivatives in the leaving group. The changes in the alkoxyl radical structure of inhibitor molecules act on their efficacy only with respect to the mammal enzymes ("group" inhibitor specificity). The differences between lupinine and epilupinine derivatives were revealed. Highly specific inhibitors of different enzymes were detected among the tested compounds.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Cholinesterases/metabolism , Organophosphorus Compounds/pharmacology , Sparteine/analogs & derivatives , Alcohols/chemistry , Animals , Arthropods , Brain/enzymology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterases/chemistry , Erythrocytes/enzymology , Humans , Isoenzymes , Isomerism , Kinetics , Mammals , Organophosphorus Compounds/chemical synthesis , Sparteine/chemical synthesis , Sparteine/pharmacology , Species Specificity , Structure-Activity RelationshipABSTRACT
Literature data have been summarized on interaction of cholinesterases of some mammals and arthropods with a group of isomer derivatives of alkaloid lupini and its epimer epilupinin. As substrates of cholinesterases of several mammals there are studied 8 acetates containing in their molecules the chinolysidin bicycle with different structure of N-alkyl radical, which showed certain elements of specificity of action. For 2 isomer esters that are derivatives of the protonated base of the lupinin and epilupinin structures, differences in their substrate characteristics were revealed. The polyenzyme analysis if anticholinesterase efficiency was performed for 30 organophosphorus inhibitors that are dialkoxyphosphorus derivatives of lupinin and epilupinin; as a result, quite a few peculiarities of their action depending on their structure were revealed. Several tested compounds turned out to act as specific inhibitors of cholinesterases of some mammals and arthropods.
