Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction.

Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M. MX-1828 has statistically significant decrease of normalized rate of smooth muscle contraction for bradykinin concentrations 10-10 and 10-9 M by 20.7 and 8.6%, respectively, but for agonist concentration 10-6 M, this parameter increased by 10.7% and amplitude was reduced by 29.5%. Compounds MX-2011, MX-1785 and MX-2004 showed no natural effect on bradykinin-induced smooth muscle contraction. Compounds MX-1775, MX-1828, MX-1626 were selected for further research of their influence on kinin-kallikrein system and pain perception.

[Synthesis and antiaggregative activity of a new RGDF mimetic]. / Sintez i antiagregatsionnaia aktivnost' novogo RGDF-mimetika.

m-[4-Oxo-4-(piperazin-1-yl)butyrylamino)]benzoyl-D,L-beta-(3,4-methylenedioxyphenyl)-beta-alanine, a new mimetic of the peptide RGDF, was synthesized. This compound inhibited ADP-induced platelet aggregation in human blood plasma enriched with platelets with IC50 3.5 x 10(-8) M. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 6; see also http://www.maik.ru.

Synthesis and properties of peptidomimetics--inhibitors of platelet aggregation.

The literature data on effective approaches to the development of the novel peptidomimetics, antagonists of fibrinogen GP IIb/IIIa receptors as potential antithrombotic agents are generalized and systematized in the review. The data obtained by the authors on the synthesis and properties of novel peptidomimetics are reported.

[In vitro effect of 1,2-dihydro-3H-1,4-benzodiazepine-2-one derivatives on the platelet aggregation and lipid peroxidation in rats]. / Vliianie in vitro proizvodnykh 1,2-digidro-3H-1,4-benzdiazepin-2-ona na agregatsiiu trombotsitov i peroksidnoe okislenie lipidov u krys.

There were discovered the anti-aggregative properties of some psychotropic drugs as gidazepam, phenazepam and its derivatives 3-oxyphenazepam, esters of 3-oxyphenazepam, with IC50 values of 8.19-11 x 10(-4) M. On their anti-aggregative effects they exceed of the acetylsalicylic acid (IC50 = 21.3 x 10(-4) M). Only gidazepam, containing in its chemical structure hydrazide fragment, caused significant decrease in the content of MDA. The possibility of involvement of lipid peroxidation in mechanism of its anti-aggregative effect is discussed.

[Low-temperature fixation of electron microscopy specimens]. / Izuchenie nizkotemperaturnoi fiksatsii élektronno-mikroskopicheskikhob''ektov.

An attempt was made to estimate the quality of cryofixation by thermogram method--time relationship of object temperature during freezing and heating of the specimen while preparing it for the electron microscopic studies. The experiments carried out showed the necessity of estimating cryofixation quality to rule out artefacts appearing due to solvent crystallization.

[Changes in collagen structure under the influence of mechanical dispersion]. / Izmenenie struktury kollagena pod vliianiem mekhanicheskogo dispergirovaniia.

Air-dry collagen isolated from cattle retinal layer by means of alkaline-salt treatment was crushed in a laboratory vibro-mill at 80-150 degrees K. Mechanochemical transformations were studied by means of viscosimetry, polarimetry, ESR-spectroscopy and electron microscopy. Mechanical tensions induce breakage of covalent bonds of polypeptide chains, accompanied by a decrease of protein molecular mass, and of lateral interactions, which results in loosening of collagen structure and partial denaturation.