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Biomedical subjects

V B Sokolov

Publications and source records attributed to V B Sokolov.

15 recordsLinked to original sources
PubMed1998

[A new inhibitor of pyrimidine phosphorylase].

5,5-Bis(hydroxymethyl)-2-oxo-[1-(2-trifluoromethyl)-3,3,3- trifluoropropionamido)-1-trifluoromethyl-2,2,2-trifluoroethyl- 1,3,2-dioxaphosphan (CA-423) is an in vitro inhibitor of the Escherichia coli uridine and thymidine phosphorylases. Unlike widely studied nucleoside analogues, this compound binds to the enzymes irreversibly. Its LD50 in mice was 40 mg/kg. Due to the involvement of pyrimidine phosphorylases in carcinogenesis and the relatively low toxicity of CA-423, it is promising for anticancer therapy.

Animals↗
PubMed1992

[Inhibition of enzymatic activity of alpha-thrombin by low molecular weight synthetic inhibitor].

The effect of the organophosphoric inhibitor, SA-152, on the fibrinogen-coagulating and TAME-esterase activity of bovine alpha-thrombin was studied. The irreversible inhibition constants (k11 = 1.1 x 10(4) M-1.min-1,Ki = 0.7 x 10(-4) M, k2 = 0.8 min-1 towards the coagulating activity and kII = 0.7 x 10(4) M-1.min-1, Ki = 0.3 x 10(-4) M, k2 = 0.2 min-1 towards the esterase activity) were determined. The SA-152 inactivated alpha-thrombin was dialyzed and incubated with 0.5 M and 2.5 M NaCl and 10 mM TAME. There was no reconstitution of activity of the SA-152 modified alpha-thrombin after dialysis and treatment with high concentrations of NaCl and TAME. Heparin interactions with the anion-binding site of the high molecular weight recognition center in the alpha-thrombin molecule did not significantly influence the values of the kinetic constants for the enzyme inhibition by SA-152. This finding is consistent with the hypothesis on the irreversible binding of SA-152 in the active center of the enzyme.

Animals↗
PubMed1991

[Effects of gamma-aminobutyric acid antagonist, 4-ethyl bicyclo-phosphate, on total and synaptic evoked responses in neurons of hippocampal slices].

Influence of 4-E-BPE on the amplitude of population spices (PS) evoked in CA1 area by Shaffer collateral stimulation in hippocampal slices were analysed. Bath application of 4-E-BPE (10(-6)-10(-5) M) led to a pronounced increase in the amplitude of the PS, the appearance of secondary PS and then introduction of GABA led to restoring original state. The 4-E-BPE was more potent than picrotoxin. These findings suggest that 4-E-BPE suppress inhibitory synaptic transmission in the CA1 region of hippocampus.

Animals↗
PubMed1990

[Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid].

A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Acetylcholinesterase↗
PubMed1989

[The effect of synthetic proteinase inhibitors of the level of human recombinant proinsulin production, secreted by a genetically engineered strain of Bacillus subtilis].

Influence of O,O,-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)amino-1- methylpropylphosphonate and O,O-diisobutyl-1-[2-(ethoxycarbonyl)aminoperfluoroprop-2-yl] -1- methylpropylphosphonate on the level of production of human proinsulin secreted by a genetically engineered culture Bacillus subtilis AJ 73 (pBINS1.0.) has been studied. The above phosphonates, being non-toxic for microorganisms, reduced degradation of proinsulin by serine proteinases.

Animals↗
PubMed1989

[The effect of dimethyl sulfoxide on the thromboelastographic indices and the microcirculation in patients with rheumatic diseases].

Using a blind method for assessing the results, a study was made of the effect of dimethylsulfoxide (DMSO) on fibrin formation and microcirculation in 42 patients with rheumatic diseases (rheumatoid arthritis, systemic scleroderma, Raynaud's syndrome). It has been shown that the therapeutic effect of DMSO in rheumatic diseases is determined to a definite degree by its normalizing action on fibrin formation and microcirculation.

Dimethyl Sulfoxide↗
PubMed1987

[Interaction of dialkyl(alpha-carbomethoxy-beta,beta,beta-trifluoro- ethyl) phosphates with mammalian esterases].

The interaction of dialkyl (alpha-carbometoxy-beta,beta,beta-trifluoroethyl) phosphates (RO)2P(O) . OCH(CF3)COOMe (R = Me, Et, Pr, Pri, Bu, Bui, Am, Hex) (I-VIII) with human erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase, pig liver carboxylesterase was studied and acute toxicity in mice was estimated. Compounds (I)-(VIII) were not hydrolyzed by carboxylesterase, slowly and irreversibly inhibited acetylcholinesterase (kII = 10(2)-10(4) M-1 X min-1) and more efficiently inhibited butyrylcholinesterase and carboxylesterase (kII = 10(3)-10(7) M-1 X min-1). The structure--antienzymatic activity relationships were investigated. With increasing of hydrophobicity of alkoxy groups, antienzymatic activity to butyrylcholinesterase and carboxylesterase ("sites of loss") rises equally and more significantly, than antiacetylcholinesterase activity (delta lg kII 1.0 and 2.4 for R = CH3 and C5H11 resp.). Branching at the alpha-position of alkoxy groups leads to sharp reducing of acetylcholinesterase and butyrylcholinesterase inhibition constants, the carboxylesterase inhibition mechanism becoming reversible. Multiple regression analysis (the Kubinyi model) showed that influence of steric hindrances is revealed at the phosphorylation stage. It was found that phosphates (I)-(VIII) possess low acute toxicity in mice (900-2000 mg/kg). The toxicity of this homologous series appears to be independent of the hydrophobicity. Role of esterases in toxicological effect of compounds (I)-(VIII) is discussed.

Acetylcholinesterase↗
PubMedDate not supplied

[Comparative study of the interaction of acetylcholinesterases of human erythrocytes and the heads of houseflies with phosphorylated alkylchloroformoximes].

Studies have been made on the interaction of four types of phosphorylated alkylchloroformoximes, i.e. analogues of an insecticide-acaricide valexon, with acetylcholinesterases from human erythrocytes and from the heads of the housefly Musca domestica. Antiacetylcholinesterase activity of the drugs depended both on the structure of the organophosphorus compounds, and the origin of the enzyme, indicating the existence of differences in the active surface of these acetylcholinesterases. Incorporation of one or two chloride atoms into alkylchloroformoxime group of the cleaved part of the organophosphorus compounds increased anticholinesterase activity with respect to both enzymes. Diethyl derivatives of these drugs exhibited higher specificity with respect to housefly enzyme as compared to human acetylcholinesterase.

Acetylcholinesterase↗
PubMedDate not supplied

[Dental forceps].

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Dental Instruments↗