Physicochemical study of biomolecular interactions between lysosomotropic surfactants and bovine serum albumin.

The interactions between two cationic lysosomotropic surfactants (2-dodecanoyloxyethyl)trimethylammonium bromide (DMM-11) and (2-dodecanoyloxypropyl)trimethylammonium bromide (DMPM-11) with bovine serum albumin (BSA) in Hepes buffer (pH=7.4) were systematically studied by surface tension, fluorescence and circular dichroism (CD) spectroscopy and isothermal titration calorimetry (ITC). Furthermore, the size of the micellar aggregates and the polydispersity indexes of both cationic surfactants were studied by dynamic light scattering technique (DLS).

Hydrolysis driven surface activity of esterquat surfactants.

Hypothesis: Surface activity of selected cleavable esterquat cationic surfactants is determined by the synergistic effect of surface active products of their hydrolysis.

Experiments: Interfacial behavior of two classes of esterquat surfactants, quaternary alkylammmoniumesters and amino acid betaine (trimethylglycine) esters of fatty acids were examined both experimentally and theoretically. The surface tension measurements at air/water interface were performed by the pendant drop shape analysis method, then the obtained isotherms were theoretically described by the model of adsorption of ionic/non-ionic surfactants mixtures taking into account the presence of surface active products of surfactant hydrolysis.

Antifungal activity of gemini quaternary ammonium salts.

A series of gemini quaternary ammonium chlorides and bromides with various alkyl chain and spacer lengths was synthesized. The most active compounds against fungi were chlorides with 10 carbon atoms within the hydrophobic chain. Among these compounds were few with no hemolytic activity at minimal inhibitory concentrations.

Gemini ester quat surfactants and their biological activity.

Cationic gemini surfactants are an important class of surface-active compounds that exhibit much higher surface activity than their monomeric counterparts. This type of compound architecture lends itself to the compound being easily adsorbed at interfaces and interacting with the cellular membranes of microorganisms. Conventional cationic surfactants have high chemical stability but poor chemical and biological degradability.

Surface properties of the derivatives of lysosomotropic substances against other quaternary ammonium salts.

Equilibrium adsorption at the air/water interface of cationic surfactants belonging in the group of quaternary ammonium bromides was studied. Quaternary ammonium salts, derivatives of lysosomotropic substances with different alkyl chain numbers and hydrophobicities were investigated. Surface properties of considered compounds, were examined and presented against other quaternary ammonium bromides of different chemical structure and with different number of alkyl chains in the molecule.

Biological activity of new N-oxides of tertiary amines.

Potential biological properties of newly synthesized single and double alkyl chain N-oxides of tertiary amines (NTA) were studied. Individual compounds in each of the series had alkyl chains of different length. Various experiments were performed to determine a mechanism of the interaction between NTA and model and biological membranes.

Antioxidative activity of new N-oxides of tertiary amines: membrane model and chromogen studies.

Potential antioxidative activities of three series of newly synthesized N-oxides were studied. Individual components in each of the series differed in the lipophilicities and number of free radical scavenging groups. Various methods were used to determine their antioxidative efficiencies: Prevention of erythrocyte membrane lipid oxidation induced by UV irradiation and chromogen experiments in which antioxidative efficiencies of compounds were compared to that of the standard antioxidant Trolox (a water-soluble vitamin E analogue).

Hemolysis of erythrocytes and erythrocyte membrane fluidity changes by new lysosomotropic compounds.

This work contains the results of studies on the influence of newly synthesized lysosomotropic substances (lysosomotropes) on human erythrocytes. Six homologous series of the compounds differing in the alkyl chain length and counterions were studied. They were found to hemolyse erythrocytes and to change their osmotic resistance.

The aminoesters as inhibitors of plasma membrane H+-ATPase in the yeast Saccharomyces cerevisiae.

A set of oxalates of alpha-dimethylamino fatty acids n-alkyl esters (MEM-ns and n-MEM-8s) and n-dodecyl-N,N-dimethylalaninate (DMAL-12s) were synthesized. Their activities on the growth, transport, and ATPases from the yeast Saccharomyces cerevisiae were compared. The compounds differ in the number of carbon atoms in their aliphatic chain and in the position of that chain in their molecular structure.

The sensitivity of yeast and yeast-like cells to new lysosomotropic agents.

The lysosomotropic action of the compounds DM-11 and DMAL-12s against Saccharomyces cerevisiae, Schizosaccharomyces pombe and Candida albicans is species- and pH-dependent. At pH 6.0, DMAL-12s is less effective against S.

The dual mechanism of the antifungal effect of new lysosomotropic agents on the Saccharomyces cerevisiae RXII strain.

Quinacrine was used to visualize the intracellular pH changes in the yeast strain Saccharomyces cerevisiae RXII occurring after exposure to four recently-synthesized lysosomotropic drugs: DM-11, PY-11, PYG-12s and DMAL-12s. The cells took up quinacrine, mostly accumulating it in their vacuoles. DM-11 and PY-11 gave rise to diffuse quinacrine fluorescence throughout the cells, with the vacuoles staining to a somewhat greater extent than the cytosol.

Lysosomotropic N,N- dimethyl alpha-aminoacid N-alkyl esters and their quaternary ammonium salts as plasma membrane and mitochondrial ATPases inhibitors.

A set of n-alkyl esters of N,N-dimethylglycine (DMG-n) and their methobromides (DMGM-n) was synthesized, and their activities on yeast Saccharomyces cerevisiae were compared. The compounds differ in the number of carbon atoms in the aliphatic chain. Aminoesters with 12 carbon atoms appeared to be most active.

Comparative studies of the biological activities of lysosomotropic aminoesters and quaternary ammonium salts on the yeast Saccharomyces cerevisiae.

The biological activity of lysosomotropic n-alkyl N,N-dimethylglycinates (DMG-n) was compared with that of a quaternary ammonium salt IM (methochloride of DMG-12). The activity of the glycinates appeared to be carbon chain length dependent and was similar at pH 6 and pH 8. Nutritional auxotrophy and respiratory deficiencies have no influence on DMG-n sensitivity.

In vivo characterization of the drug resistance profile of the major ABC transporters and other components of the yeast pleiotropic drug resistance network.

Multidrug resistance (MDR) mediated by broad specificity transporters is one of the most important strategies used by pathogens, including cancer cells, to evade chemotherapy. In the yeast Saccharomyces cerevisiae, a complex pleiotropic drug resistance (PDR) network of genes involved in MDR is composed of the transcriptional regulators Pdr1p and Pdr3p, which activate expression of the ATP-binding cassette (ABC) MDR transporters-encoding genes PDR5, SNQ2, and YOR1 as well as other not yet identified genes. We have screened 349 toxic compounds in isogenic S.

Influence of some lysosomotropic compounds on calcium ion desorption process from liposome membrane.

The effect of a group of model lysosomotropic compounds on the process of Ca2+ ion desorption from lecithin liposome membranes was studied. The compounds studied were: hydrochlorides of fatty acids 2-dimethylaminoethyl esters (DM-n) for n = 9, 11, 13 and 15 carbon atoms in the fatty acid alkyl chain and methochloride of 2-dimethylaminoethyl laurate (DMS-11). It was found that all the compounds studied caused increased desorption with increasing concentration of the compound.

Hemolytic activity of aminoethyl-dodecanoates.

The effect of new lysosomotropic compounds on red blood cell hemolysis and erythrocyte membrane fluidity has been investigated. In earlier studies it was shown that the compounds inhibit the growth of yeast and plasma membrane H(+)-ATPase activity. The study was performed with eight aminoethyl esters of lauric acid variously substituted at nitrogen atom.