[The role of cytochrome p450 in metabolism of S-ethynylthiophosphates].

We studied interaction between S-ethynyl ethers of phosphorus acids with cytochrome P-450 from rat liver and housefly abdomen. High thionic effect, i.e.

[Mechanism of the "acetylene effect" during interaction of organophosphorus compounds with cholinesterases].

Here we present data on the anticholinesterase activity of 58 synthesized ethers of phosphorus thioacids with an acetylene bond in the thioether group. Anticholinesterase activity of the compounds, with acetylene group in beta and especially alpha position, in the thioether radical is many times that of their saturated analogs. Reaction between the enzymes and acetylene organophosphorous inhibitors, as well as their saturated analogs, results in phosphorylated enzyme.

[Mechanism of action of 2-aryloxy-2-thio-1,3,2-oxazaphosphorinane pesticides].

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.

[Mechanism of action of thiophosphoroorganic insectoacaricides containing fragments of N-carbaalkoxylated amino acids].

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].

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.

[Anticholinesterase activity of certain carboranyl-containing thio- and selenoesters of pentavalent phosphorus acids].

Anticholinesterase activity of carboranyl containing thio- and selenoesters of pentavalent phosphorus acids has been studied. Insertion of the carboranyl substituents in the thioester group of phosphororganic compounds was found to increase the anticholinesterase activity as compared with the thioalkyl analogues. The compounds with B-carboranyl group are less active inhibitors of cholinesterase than their isomers with C-carboranyl group.

[The mechanism of anticholinesterase action of acetylene organophosphorus inhibitors].

Introduction of the triple bond in the leaving group of the organophosphorus inhibitor molecule gives a sharp raise of the inhibitor activity but does not change principal characteristics of the cholinesterase inhibition mechanism. The reactivation experiments suggest that inactivation of cholinesterases by these compounds occurs due to phosphorylating of the serine hydroxyl by the corresponding phosphoric acid. A close similarity was shown between acetylenic and saturated organophosphorus inhibitors in altering ka upon change of pH and tetraalkylammonium ions action.

[Effect of substituted thiobutinylic esters of phosphorus thio acids and their saturated analogs on cholinesterases of different origins].

Studies have been made of the effect of organophosphorus inhibitors (OPI) containing butynilic group in the detectable part of the molecule, and of their saturated analogues on cholinesterases from different species of mammals and arthropods. In all cases without a single exception, acetylene compounds exhibited higher anticholinesterase effect than saturated ones. The value of "acetylene effect" varied to a great extent and depended on both the structure of OPI and the source of cholinesterase, these data indicating the existence of differences in the structure of the active site in cholinesterases investigated.

[Capacity of diphosphonates to bind calcium and their effect on the osmotic permeability of the frog bladder wall].

Like EDTA, diphosphonates increase permeability of the frog urinary bladder wall for water osmotic gradient. Their effect is proportional to the stability of their binding with calcium ions. The efficacy of diphosphonates falls upon pH decline.

[Stereospecific action of organothiophosphate amino acid derivatives on nervous system esterase activity in the cockroach].

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.

[Analysis of kinetics of the combined inhibition of cholinesterases].

In the paper the analysis of the possible kinetic schemes is performed for the process of the combined inhibition of cholinesterases. It is shown that the considered schemes result in the identical experimental dependencies of the inhibition constants from the concentration of the inhibitor. Based on the analysis of about 200 experiments a linear dependence was found between logarithms of constants describing the reversible and irreversible action of the inhibitor.

Prospects for developing and improving a chemical method of pest control in the next 10 to 15 years.

The assortment of chemical substances for pest control which exists in the world or is planned by us, and the reserves which exist in scientific research make it possible to assert that: 1) It is possible to produce an assortment of pesticides that is practically harmless for man and useful animals; 2) it is possible to eliminate the accumulation of pesticides and their residue in the environment, in food products, and in food chains; 3) it is possible to produce highly selective pesticides which will not damage useful inhabitants of the biosphere, particularly useful arthropods and soil microorganisms; 4) it is possible with the proper technical approaches, especially with proper alternation of pesticides, to avoid the development of resistant strains of pests. This requires continuation of intensive scientific and technical investigations both of the pesticides themselves and in producing integrated systems with the use of an entire complex of means and methods for protecting the harvest, and improving the technical means of application.