[Interaction with esterases and mechanism of synergistic action of thio- and dithiophosphates containing the fragments of N-acylated glycine and beta-alanine]. / Vzaimodeistvie s ésterazami i mekhanizm sinergisticheskoi aktivnosti tio- i ditifosfatov, soderzhashchikh fragmenty N-atsilirovannykh glitsina i beta-alanina.

We studied the interaction between O,O-diethyl-S-[(N-acyl-N-alkoxycarbonylalkyl)aminomethyl]thiophosphates and mammalian cholinesterases as well as esterases from insect tissue extracts by kinetic methods and disc electrophoresis. The coefficients of combined effect of these compounds or their dithioanalogs with permethrin were determined. The obtained data suggest that the synergistic effect on the common cockroaches and houseflies is chiefly due to carboxylesterase inhibition by monothioderivatives and monooxygenase suppression by dithioderivatives, respectively.

[Specific interaction between esterases and 2-butylthio-2-thio-1,3,2-oxazaphosphorynane and its cyclic and acyclic analogs]. / Osobennosti vzaimodeistviia s ésterazami 2-butiltio-2-tio-1,3,2-oxsazafosforinana i nekotorykh ego tsiklicheskikh i atsiklicheskikh analogov.

We studied the anticholinesterase and anticarboxylesterase effects of 1,3,2-oxazaphosphorynane derivatives and certain cyclic and acyclic analogs on the two enzymes of homoiotherms (ACE from human erythrocytes and BuCE from horse serum) as well as the enzymes from insect tissues (the nerve cord of the American cock-roach and the cephalic region of the domestic fly). The differences in in vitro antiesterase activity of cyclic thionic and the corresponding oxo derivatives of phosphorinane were revealed. The mechanism of the esterase active center phosphorylation not only splitting off the outgoing group (in vivo) but also opening the cycle by P-O bond (in vitro and possibly in vivo) is usually proposed to explain the higher inhibiting activity of the thionic compounds compared to the oxonic ones. The possible involvement of this phosphorylation mechanism in the synergistic activity of the studied compounds is discussed.

[Mechanism of action of 2-aryloxy-2-thio-1,3,2-oxazaphosphorinane pesticides]. / Issledovanie mekhanizma deistviia pestitsidov riada 2-ariloksi-2-tio-1,3,2-oksazafosforinana.

The interaction of 2-aryloxy-2-thio-1,3,2-oxazaphosphorinanes exhibiting nematocide, insecticide/acaricide, and synergetic activities with monoamine oxidases and the interaction of the corresponding oxones, 2-aryloxy-2-oxo-1,3,2-oxazaphosphorinanes, with various cholinesterases, carboxyl esterases, and monoamine oxidases were studied. We showed that the thioderivatives inhibited monoamine oxidases, whereas oxones, which are, as a rule, weak cholinesterase inhibitors, strongly inhibited carboxyl esterases of the American cockroach and were transformed with monoamine oxidases into the strong cholinesterase inhibitors, acyclic phosphamidates. This allowed us to explain the low toxicity of the thioderivatives, the high toxicity of the oxoderivatives, and the great difference in toxicities of thio- and oxocompounds in the 1,3,2-oxazaphosphorinane series. The capacity of thioderivatives to inhibit monoamine oxidases and of oxoderivatives and their further activation products to inhibit carboxyl esterases, i.e., both enzymes responsible for pyrethroid detoxication in insects, explains the synergetic activity of the 1,3,2-oxazaphosphorinane series.

[Mechanism of action of thiophosphoroorganic insectoacaricides containing fragments of N-carbaalkoxylated amino acids]. / Issledovanie mekhanizma deistviia tiofosfororganicheskikh insektoakaritsidov, soderzhashchikh fragmenty N-karbalkoksilirovannykh aminokislot.

Toxicity and insecticide and acaricide activity of compounds (1) is significantly dependent on the nature of amino acid (n = 1 or 2) and substituents in carbamate and amino acid ester groups (R and R1). Investigation of interaction of these compounds with mammalian carboxylesterases, and the appropriate "oxones" with choline esterases of mammal and arthropoda revealed that the lower toxicity and activity of beta-alanine derivatives (n = 2) compared with glycine derivatives (n = 1) are due to the more rapid hydrolysis by carboxylesterases (detoxication). The low toxicity of dithiophosphonate with R = Me, R1 = Bu(i), n = 1 and the high toxicity of its isomer with R = Bu(i), R1 = Me, n = 1 are associated with the more rapid oxidative cleavage of isobutyl group in comparison with the other substituents, because detoxication occurs by the cleavage of R1 and activation--by that of R respectively.

[The interaction of phoscarban with the esterases of houseflies and synanthropic cockroaches]. / Vzaimodeistvie foskarbana s ésterazami komnatnykh mukh i sinantropnykh tarakanov.

Interactions of phoscarban and its "oxon" with the esterase complex of the house-fly imago and four species of synanthropic cockroaches were studied. Phoscarban and its oxon have a wide spectrum of effects on the esterase complex in cockroaches and flies. These compounds are not specific inhibitors of any of the zones of esterase activity. Their insecticide effect depends on their ability to inhibit both choline esterases, which are responsible for nervous activity, and carboxyl esterases, which are involved in the detoxication of these compounds. We studied the species specificity of the esterase complex, including individual types and fractions, to phoscarban and its oxon in the order Dictyoptera. It was especially distinct for membrane-bound and water-soluble forms of choline esterases.

[Interaction of various dithio- and thiophosphates containing amino acid fragments with carboxylesterase from rat liver]. / Vzaimodeistvie nekotorykh ditio- i tiofosfatov, soderzhashchikh fragmenty amino kislot, s karboksilésterazoi iz pecheni krysy.

The interaction of insecto-acaricides of the general formula (EtO)2P(S)SCH2CONH(CH2)nCH(R1)COOR2 and their activation metabolites (P = O analog) and detoxication products (R2 = H) with rat liver carboxylesterase was studied. The beta-alanine derivative (n = 1, R1 = H, R2 = Et) was rapidly hydrolyzed by carboxylesterase. The valine derivative (n = 0, R1 = H, R2 = Et) was hydrolytically stable, due to steric hindrances imposed by the isopropyl group, and proved to be a reversible competitive inhibitor of carboxylesterase. The corresponding monothiophosphates were not hydrolyzed by carboxylesterase, but inhibited it irreversibly. It was found that monothiophosphate derivatives of R- and S-valine irreversibly inhibit carboxylesterase, R-enantiomer being somewhat more active than S-antipode. On the other hand, under the conditions of reversible inhibition by the corresponding dithiophosphates, S-enantiomer was more active. Using model compounds, (R)- and (S)-N-chloroacetyl valine ethyl esters, it was shown that both on irreversible and reversible inhibition the differences in stereospecificity can be attributed to changes in the inhibitor orientation in the enzyme active site.

[Stereospecific action of organothiophosphate amino acid derivatives on nervous system esterase activity in the cockroach]. / Stereospetsifichnost' deistviia tiofosfororganicheskikh proizvodnykh aminokislot na ésteraznuiu aktivnost' nervnoi tkani.

The effect of optic isomers of Rp- and Sp-CH3(C2H5O)P(O)SCH2C(O)NHCH5-COOC2H5(EH-13), Rc- and Sc-(C2H5O)2P(O)SCH2C(O)NHCH (i-C3-H7)COOC2H5.(SH.-156), RpRc-, SpSc-, and SpRc-CH3(C2H5O)P(O) SCH2C(O)NHCH(i-C3H7)-COOC2H5(Sh.-142) on the fraction composition of esterases from the nervous tissue of American cockroach was investigated. Esterases were separated by polyacrylamide gel disc-electrophoresis. Sp-(EH-13) and Rc-(Sh.-156) were shown to inhibit carboxy esterase to a greater extent than their antipodes. Stereoisomers of the substance (Sh.-142) were found to influence activity of carboxy esterase molecular forms in a different way. It is postulated that the active surface of molecules of certain carboxy esterase isoenzymes may have stereospecific structure.