Synthesis and structure-activity relationship of methyl-substituted indolo[2,3-b]quinolines: novel cytotoxic, DNA topoisomerase II inhibitors.

In furtherance of our SAR study on the chemistry and antitumor activity of fused nitrogen heteroaromatic compounds, a series of linear, methyl-substituted derivatives of 5H- and 6H-indolo[2,3-b]quinolines were synthesized according to the modified Graebe-Ullmann reaction. To establish the relationship between the physicochemical and biological activities of indolo[2,3-b]quinolines, their lipophilic properties, cytotoxic and antimicrobial activity, and ability to induce topoisomerase II dependent pSP65 DNA cleavage in vitro were investigated. We found that the antimicrobial and cytotoxic activity of indolo[2,3-b]quinolines was strongly influenced by the position, and the number of methyl substituents and the presence of methyl group at pyridine nitrogen was essential for the cytotoxicity of these compounds.

Influence of plasma modification on biological properties of poly(ethylene terephthalate).

Poly(ethylene terephthalate) film was modified with argon or perfluorohexane plasma to obtain hydrophilic or hydrophobic surfaces, respectively. Various biological experiments in vitro and in vivo were chosen in order to evaluate the influence of such treatment on biocompatibility. Plasma modification does not cause toxic effects and does not influence disadvantageously the tested polyester biocompatibility.

Insect growth regulators. XXV. Chemical approach to the correlation of dynamic structure and biological activity of juvenile hormone analogues.

On the basis of flexibility of the carbon skeleton of a juvenoid molecule, an analysis of its steric properties required to induce a biological effect in insects Dysdercus cingulatus and Tenebrio molitor, is presented. Steric analyses of "branched" juvenoids and some derivatives of farnesoic acid differing in position of the double bonds, are also described.

Mutational analysis of the interaction between ecdysteroid receptor and its response element.

The interaction between the partially purified ecdysteroid receptor (EcR) and the mutated ecdysteroid-response element (EcRE) from the hsp27 gene promoter was studied using the gel retardation competition assay. The results suggest that the EcR-hsp27 EcRE contact sites are made predominantly by base pairs which are at positions -7, -6, -5, -2, -1 and +2, +5, +6 of the hsp27 EcRE palindrome. An increase or decrease in the spacing between the half-palindromes reduces the affinity of the hsp27 EcRE to the receptor, while a mutation of the central A/T base pair to C/G has practically no effect on EcR binding.

Antibacterial activity of phosphono peptides based on 4-amino-4-phosphonobutyric acid.

Phosphono dipeptides based on 4-amino-4-phosphonobutyric acid (phosphonic acid analogue of glutamic acid, GluP) were synthesized and evaluated for their antibacterial activity. Dipeptides containing N-terminal alanine, leucine, isoleucine, phenylalanine or lysine showed marked antibacterial activity against Escherichia coli, whilst those containing alanine, leucine, valine or proline were active against Serratia marcescens. AlaGluP and LeuGluP were nearly equipotent with the respective dipeptides based on 1-aminoethylphosphonic acid (phosphonic acid analogue of alanine).

Biomechanical investigation of the hyoid bone using speckle interferometry.

Speckle interferometry is a non-destructive measurement technique using a laser. The principles of the method are described. Human hyoid bones (n = 10) were investigated.

Effect of the electret-blood contact time on the adhesion of human blood platelets.

The paper presents the results of research into the time characteristics of adhesion of platelets to the electret surface made from polyethylene terephthalate PET foil of 36 microns thickness. The electrets were formed by using the electron beam method. The method based on the electrostatic induction phenomenon was utilized to measure the electric charge surface density.

Effect of electric charge on the adhesion of human blood platelets.

The paper presents the results of research into the effect of the size and depth of the implanted electric charge on the adhesion of human blood platelets. The experiments were carried out on polyethylene terephthalate PET foil of 36 microns thickness. The electret formation process was carried out in an electron-beam device.

Immobilization of penicillin acylase on copolymer of butyl acrylate and ethylene glycol dimethacrylate.

The effects of glutaraldehyde, enzyme concentrations and reactants volumes, ionic strength, pH value and carrier particle diameter on immobilization of penicillin acylase onto acrylic carriers were studied. The activity of immobilized enzyme preparations was also studied over a range of pH values and temperatures and thermal and pH stabilities were determined. The use of the immobilized preparation for penicillin G hydrolysis in a batch reactor was investigated.

Effect of polymer matrix on penicillin acylase immobilization on copolymers of butyl acrylate and ethylene glycol dimethacrylate.

Copolymers of butyl acrylate and ethylene glycol dimethacrylate with various degree of crosslinking and aminolysis were used for penicillin acylase immobilization. The amount and activity of the bound protein decreased with the decrease of crosslinking when copolymers having nearly constant degrees of aminolysis were compared. The increase of the carrier amino group content increased the ability to bind the protein (by glutaraldehyde method) without a proportional rise of enzyme activity.

Inhibition of aminopeptidases by phosphonic acid and phosphinic acid analogues of aspartic and glutamic acids.

More than 30 phosphonic and phosphinic acid analogues of aspartic and glutamic acids were synthesized in order to probe how the structural differences of these molecules were reflected in their ability to inhibit cytosolic (LAP) and microsomal (APM) aminopeptidases. Although most of the compounds studied were found to exert only a modest inhibitory effect, the studies provide some information on the structural requirements of the binding subsites and catalytic centers of both enzymes.

Critical cell volume and shape of bovine erythrocytes.

The relationship between erythrocyte shape and the critical cell volume was investigated. Agents able to increase the critical cell volume induced three main stable shapes of erythrocytes: discocytic, stomatocytic, and echinocytic. The absence of correlation between shape and critical cell volume under isoosmotic conditions suggests that relative differences between the surface areas of the inner and the outer leaflet of the cell membrane do not influence the critical volume of a cell.

Organophosphonate utilization by the wild-type strain of Pseudomonas fluorescens.

The wild-type strain of Pseudomonas fluorescens was found to utilize a range of structurally diverse organophosphonates as its sole carbon or nitrogen sources. Representative compounds included aminoalkylphosphonates, hydroxyalkylphosphonates, oxoalkylphosphonates, and phosphono dipeptides. Among them, amino(phenyl)methylphosphonate,2-aminoethylphosphonate, aminomethylphosphonate, diisopropyl 9-aminofluoren-9-ylphosphonate, and 2-oxoalkylphosphonates were used by P.

The effect of arsenate and vanadate ions on the critical cell volume of bovine erythrocytes.

Arsenate, used as an inhibitor of glycolysis, decreases the critical cell volume of erythrocytes, whereas orthovanadate, used as an accelerator of dephosphorylation of phosphatidyl-inositol-4,5-biphosphate, exerts an opposite effect. The ATP-dependent changes of the critical cell volume do not depend on the phosphorylation state of phosphatidylinositol. An interaction of the membrane skeleton with the lipid-protein matrix has been proposed as a regulation mechanism of the critical cell volume of erythrocytes.

Conformational change of the haemolymph juvenile-hormone-binding protein from Galleria mellonella (L).

A juvenile-hormone-binding protein (juvenile-hormone carrier), isolated from Galleria mellonella haemolymph, was treated with trypsin, chymotrypsin, carboxypeptidase A and subtilisin. Among these enzymes, only subtilisin was able to affect juvenile-hormone-binding activity of this protein. With SDS/PAGE it was shown that juvenile-hormone-binding protein, a 32-kDa peptide, is first slowly converted into a 30-kDa molecule, then into two or three smaller-molecular-mass species (20-25 kDa), which in turn were further digested to small peptides undetectable in PAGE.

Flotation of Streptomyces pilosus after lead accumulation.

The flotation of Streptomyces pilosus was studied in the absence and presence of adsorbed Pb(II) ions on the cell walls and with and without using sodium dodecylsulfate (SDS) as collector. Adsorption of SDS onto the organism in the absence and presence of Pb(II) ions was also investigated. It was found that in the absence of adsorbed Pb(II), very little flotation took place with or without the presence of SDS although SDS adsorbed to some extent on the organism.

Purification and some properties of Pseudomonas fluorescens lipase.

Lipase (triacylglycerol lipase, EC 3.1.1.

The metabolism of anthracene and 9,10-dimethylanthracene by bacteria isolated from waters.

The metabolism of two polycyclic aromatic hydrocarbons i.e. anthracene and 9,10-dimethylanthracene by Micrococcus sp.

Phosphonic and phosphinic acid analogues of tyrosine and 3,4-dihydroxyphenylalanine (dopa) as potential antimelanotic agents.

Phosphonic acid and phosphinic acid analogues of tyrosine and 3,4-dihydroxyphenylalanine (dopa) were found to influence tyrosinase activity, thus being potential regulators of melanization in mammalian cells. The analogues were tested for their cytostatic activity in vitro, by means of total cell protein determination, on mouse B16 melanoma and, for comparison, on human KB carcinoma cell lines. Four compounds out of 22 revealed promising cytostatic activity for both cell lines, being nearly equipotent with dopa.

Galvanic couples of 316L steel with Ti and ion plated Ti and TiN coatings in Ringer's solutions.

Steel 316L was coated with titanium or titanium nitride by ion plating. The tightness of the coatings was examined electro-chemically. The galvanic effects for the galvanic couples steel-titanium, steel-titanium-coated steel and steel-titanium nitride-coated steel were studied.

Antibacterial activity of phosphono dipeptides based on 1-amino-1-methylethanephosphonic acid.

Phosphono dipeptides containing 1-amino-1-methylethanephosphonic acid (phosphonic acid analogue of alpha-methylalanine, MeAlaP) and glycine, alanine, valine, leucine phenylalanine, proline, methionine or lysine as N- terminal component were synthesized in order to determine their antibacterial properties. Peptides containing alanine, leucine, valine phenylalanine and methionine showed marked in vitro activity, especially against Escherichia coli and Serratia marcescens strains. There were, however, generally less potent than the respective phosphono dipeptides based on 1-aminoethanephosphonic acid (phosphonic acid analogue of alanine, AlaP).

Effect of the level of ATP and of the state of spectrin on osmotic properties of bovine erythrocytes.

The effect of the intracellular level of ATP and of the state of spectrin on the critical cell volume of bovine erythrocyte was studied. The state of spectrin was changed by thermal denaturation, which for the bovine red cell took place at similar temperature as for the human erythrocyte. The increase of the ATP level and the spectrin denaturation increased the critical cell volume, while metabolic starvation decreased it.

The effect of ATP on the order and the mobility of lipids in the bovine erythrocyte membrane.

The order and the mobility of the lipids in the membrane were measured by the ESR method for the erythrocytes with both normal and modified intracellular concentration of ATP. The lipid order did not depend on the ATP level, but the lipid mobility was affected by the intracellular ATP concentration. The lipid mobility was higher in the cells with a larger concentration of ATP.