ABSTRACT
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
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
Using the methods of factor and cluster analysis, the statistical treatment is performed of data on interaction of 7 cholinesterases (ChE)--human acetylcholinesterase, horse butyrylcholinesterase, cholinesterases of frog brain and of various squid species (Todarodes pacificus and Berrytheutis magister; in the latter case, individuals from three different habitats are compared)--with 141 reversible inhibitors of various structures. Statistically significant differences between ChE of squids and vertebrates are shown. The previously revealed intraspecies peculiarities of ChE in the Commander squid B. magister are statistically confirmed.
