Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity.

Twelve derivatives of hexadecylphosphocholine (miltefosine) were synthesized to determine how the position and length of the alkyl chain within the molecule influence their biological activities. The prepared alkylphosphocholines have the same molecular formula as miltefosine. Activity of the compounds was studied against a spectrum of tumour cells, two species of protozoans, bacteria and yeast.

[Flavonoids - main constituents of the leaves of Philadelphus tenuifolius Rupr. et Maxim].

The paper deals with the isolation and identification of the constituents of the leaves of Philadelphus tenuifolius Rupr. et Maxim. A methanolic extract was used to isolate quercetin-3-O-glucoside (isoquercitrin), and a butanolic extract to isolate kaempferol-3-O-glucoside-7-O-rhamnoside.

Phase behavior of the DOPE + DOPC + alkanol system.

Small- and wide-angle X-ray diffraction was used to study the effect of 1-alkanols, as simple models of general anesthetics, (abbreviation CnOH, n = 8-18 is the even number of carbons in the aliphatic chain) on the lamellar to hexagonal Lα→ H(II) phase transition in the dioleoylphosphatidylethanolamine-dioleoylphosphatidylcholine = 3 : 1 mol/mol (DOPE + DOPC) system. All studied CnOHs were found to decrease the phase transition temperature of the DOPE + DOPC system in a CnOH chain length and concentration dependent manner and thus promote the formation of the HII phase. Anesthetically active C8OH and C10OH were found to decrease the lattice parameter d of the Lα phase, however longer non-anesthetic CnOHs increased the parameter d; this effect being more pronounced with increasing CnOH concentration.

Molecular and component volumes of N,N-dimethyl-N-alkylamine N-oxides in DOPC bilayers.

The volumetric properties of fluid bilayers formed of dioleoylphosphatidylcholine (DOPC) with incorporated N,N-dimethyl-N-alkylamine N-oxides (CnNO, n=6, 10-18 is the even number of carbons in alkyl chain) were studied by vibrating tube densitometry in the temperature interval from 20°C to 50°C. It was found that the DOPC and CnNO mixed ideally in the investigated composition range and hence the molecular volumes of DOPC (VDOPC) and incorporated CnNO (VCnNO) were constant and additive within error limits. From the temperature dependencies of the molecular volumes of DOPC and CnNO their coefficients of isobaric thermal expansivities in the investigated temperature interval were obtained.

Study of interaction of long-chain n-alcohols with fluid DOPC bilayers by a lateral pressure sensitive fluorescence probe.

The excimer 1,2-dipyrenedecanoyl-sn-glycero-3-phosphatidylcholine (dipy10PC) fluorescence probe was used to determine effects of aliphatic alcohols (CnH2n+1OH, n = 12-18 is the even number of carbons in alkyl chain) on fluid dioleoylphosphatidylcholine (DOPC) +dioleoylphosphatidylserine (DOPS) bilayers in multilamellar vesicles at molar ratio DOPC/DOPS = 24.7. The excimer to monomer fluorescence intensity ratio increases with the increase of CnH2n+1OH/DOPC molar ratio and decreases with the CnH2n+1OH alkyl chain length n at a constant CnH2n+1OH/DOPC = 0.

[Analytical profile of mono[{3-[4-(2-ethoxyethoxy)-benzoyloxy]-2-hydroxypropyl}-tert-butylammonium] fumarate].

The present paper aims at a complex spectral and physicochemical evaluation of mono[{3-[4-(2-eth-oxyethoxy)-benzoyloxy]-2-hydroxypropyl)-tert-butyl-ammonium] fumarate, the potential ultra-short acting blocker of beta1-adrenergic receptors. The identity of the evaluated compound (labelled as UPB-2) was confirmed by 1H-, 13C-NMR and IR spectral data as well. The estimated physicochemical parameters included melting point data, solubility in various media, purity checking (adsorption thin-layer chromatography), surface activity determination (non-direct Traube stalagmometric method), acidobasic characteristics (pKa value determination by alkalimetric titration), log epsilon values estimation (spectrophotometrically in UV/VIS region) and a study of the influence of acidic and alkaline media towards the stability of UPB-2.

[Analytical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate].

The present paper deals with a complex spectral and physicochemical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate, a potential ultrashort acting beta1-blocker. The identity of the substance under study (labelled as UPB-1) was confirmed by 1H- and 13C-NMR spectra as well as IR spectrometry. The determined fundamental physicochemical characteristics included the determination of the melting point, solubility in a spectrum of solvents, verification of purity (adsorption thin-layer chromatography), determination of surface activity (Traube's stalagmometric method), acidobasic characteristics (pK(a) value by means of alkalimetric titration), determination of log epsilon values using spectrophotometry in UV/VIS region, as well as the evaluation of the effect of acid and basic media on the stability of the substance under the study.

Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis.

Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part.

Dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimetylammonium bromide: effect of phosphate group and environment of the ammonium cation on their biological activity.

A series of dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimethylammonium bromide have been synthesized. The prepared compounds exhibit significant cytotoxic, antifungal and antiprotozoal activities. Alkylphosphocholines possess higher antifungal activity against Candida albicans in comparison with quaternary ammonium compounds.

Oxidative injury induced by hypochlorous acid to Ca-ATPase from sarcoplasmic reticulum of skeletal muscle and protective effect of trolox.

Hypochlorous acid (HOCl) concentration-dependently decreased ATPase activity and SH groups of pure Ca-ATPase from sarcoplasmic reticulum (SERCA) of rabbit skeletal muscle with IC(50) of 150 micromol/l and 6.6 micromol/l, respectively. This indicates that SH groups were not critical for impairment of Ca-ATPase activity.

Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance.

Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress. Unexpectedly, it was found that sarcoplasmic reticulum Ca(2 +)-ATPase (SERCA) activity was elevated in muscles of rats with AA compared to controls, suggesting possible conformational changes in the enzyme. There was no alteration in the nucleotide binding site but rather in the transmembrane domain according to the tryptophan polar/non-polar fluorescence ratio.

Comparing anti-HIV, antibacterial, antifungal, micellar, and cytotoxic properties of tricarboxylato dendritic amphiphiles.

Three series of homologous dendritic amphiphiles--RCONHC(CH(2)CH(2)COOH)(3), 1(n); ROCONHC(CH(2)CH(2)COOH)(3), 2(n); RNHCONHC(CH(2)CH(2)COOH)(3), 3(n), where R = n-C(n)H(2n+1) and n = 13-22 carbon atoms--were assayed for their potential to serve as antimicrobial components in a topical vaginal formulation. Comparing epithelial cytotoxicities to the ability of these homologues to inhibit HIV, Neisseria gonorrhoeae, and Candida albicans provided a measure of their prophylactic/therapeutic potential. Measurements of the ability to inhibit Lactobacillus plantarum, a beneficial bacterium in the vagina, and critical micelle concentrations (CMCs), an indicator of the potential detergency of these amphiphiles, provided additional assessments of safety.

Oxidative impairment of plasma and skeletal muscle sarcoplasmic reticulum in rats with adjuvant arthritis - effects of pyridoindole antioxidants.

Objectives: To study possible oxidation of proteins and lipids in plasma and sarcoplasmic reticulum (SR) from skeletal muscles and to assess the effects of pyridoindole antioxidants in rats with adjuvant arthritis (AA) and to analyze modulation of Ca-ATPase activity from SR (SERCA).

Methods: SR was isolated by ultracentrifugation, protein carbonyls in plasma and SR were determined by ELISA. Lipid peroxidation was analyzed by TBARS determination and by mass spectrometry.

Effect of amphiphilic surfactant LDAO on the solubilization of DOPC vesicles and on the activity of Ca(2+)-ATPase reconstituted in DOPC vesicles.

Solubilization of large unilamellar 1,2-dioleoylphosphatidylcholine (DOPC) vesicles by N-dodecyl-N,N-dimethylamine-N-oxide (LDAO) was studied using turbidimetry. From turbidity data, the LDAO partition coefficient between the aqueous phase and DOPC bilayers was obtained. Using this partition coefficient, the LDAO:DOPC molar ratio in the bilayer was calculated and effects of LDAO on the bilayer stability, bilayer thickness and on the phosphohydrolase activity of sarcoplasmic reticulum Ca(2+) transporting ATPase (SERCA) reconstituted into DOPC were compared at the same LDAO:DOPC molar ratios in the bilayer.

Effect of some antioxidants on sarcoplasmic reticulum Ca2+-ATPase activity from rabbit skeletal muscle.

Objectives: Effects of phenolic antioxidants, synthetized (trolox, pyridoindole stobadine) and plant extracts (EGb 761 and Pycnogenol) were investigated on the activity of Ca(2+)-ATPase from sarcoplasmic reticulum (SR) of rabbit skeletal muscle to examine their potency to modulate the activity of this calcium level regulating enzyme.

Methods: SR vesicles and pure Ca(2+)-ATPase were isolated by ultracentrifugation. Ca(2+)-ATPase activity was measured spectrophotometrically by enzyme-coupled assay.

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile + DPPC mixture.

The tri-headed anionic dendritic amphiphile, 4-(2-carboxyethyl)-4-[(icosyloxycarbonyl)amino]heptanedioic acid (3CCb20), forms mixed aggregates with dipalmitoylphosphatidylcholine (DPPC) in excess water at 3CCb20:DPPC = 0.91:1 molar ratio. On heating, these mixed aggregates transform into fluid bilayers stacked in the liquid crystalline lamellar L(alpha) phase at about 40 degrees C.

Influence of N-dodecyl-N,N-dimethylamine N-oxide on the activity of sarcoplasmic reticulum Ca(2+)-transporting ATPase reconstituted into diacylphosphatidylcholine vesicles: efects of bilayer physical parameters.

Sarcoplasmic reticulum Ca-transporting ATPase (EC 3.6.1.

Effects of N-alkyl-N,N-dimethylamine-N-oxides on the activity of purified sarcoplasmic reticulum Ca(2+)-transporting ATPase.

N-alkyl-N,N-dimethylamine-N-oxides (CnNO, n = 10-20 is the number of alkyl carbon atoms) stimulate the skeletal sarcoplasmic reticulum (SR) Ca(2+)-transporting ATPase activity at low concentrations and inhibit it at high concentrations. The minimum concentration (cmin), at which CnNO inhibits the ATPase, continuously decreases up to n = 16-18 and then increases. The values of Cmin are smaller than the CnNO critical micelle concentration (cmc) for C10NO-C14NO homologs, but larger than cmc for C18NO-C20NO homologs.

Effects of non-ionic surfactants N-alkyl-N,N-dimethylamine-N-oxides on the structure of a phospholipid bilayer: small-angle X-ray diffraction study.

Effects of non-ionic surfactants N-alkyl-N,N-dimethylamine-N-oxides (C(n)NO, n is the number of alkyl carbons) on the structure of egg yolk phosphatidylcholine (EYPC) bilayers in the lamellar fluid phase was studied by small-angle X-ray diffraction as a function of H(2)O:EYPC and C(n)NO:EYPC molar ratios. The bilayer thickness d(L) and the lipid surface area at the bilayer-aqueous interface S(L) were calculated from the repeat period, d of the lamellar phase, based on the model that water and EYPC + CnNO molecules form separated layers and that their molecular volumes are additive. In the studied range of m=CnNO:EYPC molar ratios up to 1:1, d(L) and S(L) change linearly.

[Solubilization of unilamellar egg yolk phosphatidylcholine liposomes by N-alkyl-N,N-dimethylamine N-oxides].

The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine (EYPC) liposomes by a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n = 10-14 carbon atoms in the alkyl substituent) was studied using turbidimetry. The solubilizing concentration of CnNO (cS) was estimated as the CnNO concentration causing the half-maximum decrease in turbidance. From the linear cS dependence on EYPC concentration, the lipid--aqueous phase molar partition coefficient (Kp) and the CnNO:EYPC molar ratio in the CnNO + EYPC aggregates (nL:nEYPC) at cS were obtained: Kp = 82 +/- 25 and nL:nEYPC = 0.

X-ray diffraction and neutron scattering studies of amphiphile-lipid bilayer organization.

The lipid bilayer thickness d(L), the transbilayer distance of lipid phosphate groups d(pp/inf> and the lipid surface area A(L) of fluid hydrated bilayers of lamellar phases of egg phosphatidylcholine or dipalmitoylphosphatidylcholine containing N-alkyl-N,N-dimethylamine N-oxides (CnNO), 1,4-butanedi-ammonium-N,N'-dialkyl-N,N,N',N'-tetramethyl dibromides (GSn) or mono-hydrochlorides of [2-(alkyloxy)phenyl]-2-(1-piperidinyl)ethylesters of carbamic acid (CnA) were obtained by X-ray diffraction, and the bilayer thickness in extruded unilamellar dioleoylphosphatidylcholine vesicles containing C12NO was obtained by the neutron scattering. The values of d(L), d(pp/inf> and A(L) change linearly up to the 1:1 amphiphile:lipid molar ratio. The slopes of these dependencies increase for d(L) and d(pp/inf> and decrease for AL) with an increasing number of carbons n in the amphiphile long hydrocarbon substituent (18> or =n> or =8 for CnNO, 16> or =n> or =9 for GSn, 12> or =n> or =5 for CnA), while the opposite trends are observed for the short substituent (8> or =n>/=6 for CnNO, 9> or =n> or =7 for GSn, 5> or =n> or =3 for CnA).