Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ALKYLATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1992

Identification of a membrane-associated 1-0-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine hydrolyzing phospholipase A2 in guinea pig 1 epidermis. Implications in the cutaneous biosynthesis of platelet-activating factor.

A membrane-associated 1-0-alkyl-2-arachidonoyl-GPC hydrolyzing phospholipase A2 was identified in guinea pig epidermis. It is regio-specific (associated with the particulate microsomal fraction) and specific for the hydrolysis of 1-0-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine. It is sensitive to low calcium concentrations suggesting that it may be activated by increasing intracellular calcium. Since ether-linked phospholipids are known to exist in the epidermis, further understanding of the properties of this 1-0-alkyl-arachidonoyl-hydrolyzing PLA2 may allow us to control the generation of 1-0-alkyl-2-lyso-sn-glycero-3-phosphocholine, a key substrate for the generation of the platelet-activating factor in the tissue.

Animals↗
PubMedDate not supplied

Synthesis of bile acid analogs: 7-alkylated chenodeoxycholic acids.

This paper describes a method for the preparation of 7-alkylated chenodeoxycholic acids from 3 alpha-hydroxy-7-oxo-5 beta-cholanoic acid. The synthetic procedure is based upon a Grignard reaction between the keto bile acid and an alkyl magnesium halide. Under the conditions employed, the introduction of alkyl groups is highly stereoselective. Only 7 beta-alkylated epimers are obtained. The overall yield is several-fold higher than that obtained by the previous method, which involved the preparation of an oxazoline intermediate.

Bile Acids and Salts↗
PubMed1990

Uracil-DNA glycosylase activity affects the mutagenicity of ethyl methanesulfonate: evidence for an alternative pathway of alkylation mutagenesis.

Mutagenesis induced by the alkylating agent ethyl methanesulfonate (EMS) is thought to occur primarily via mechanisms that involve direct mispairing at alkylated guanines, in particular, O6-ethyl guanine. Recent evidence indicates that alkylation of guanine at the O-6 position might enhance the deamination of cytosine residues in the complementary strand. To determine whether such deamination of cytosine could play a role in the production of mutations by EMS, the efficacy of this agent was tested in uracil-DNA glycosylase deficient (Ung) strains of Escherichia coli. The Ung- strains showed a linear response with increasing doses of EMS. This response was independent of the umuC gene product. In contrast, the Ung+ strains yielded a dose-squared response that became linear at higher doses of EMS when the cells were defective for the umuC gene product. These results support a model for mutagenesis involving the deamination of cytosines opposite O6-alkylated guanines followed by an error-prone repair event.

DNA Glycosylases↗
PubMed1982

Thermochemistry of aqueous solutions of alkylated nucleic acid bases. IV. Enthalpies of hydration of 5-alkyluracils.

Enthalpies of sublimation, DeltaH degrees (subl) and of solution in water, DeltaH degrees (sol) were determined for a series of crystalline 1,3-dimethyl-uracil derivatives substituted at the C5-ring carbon atom with alkyl groups (-C(n)H(2n+1), n = 2-4) and some of their C(5.6)-cyclooligomethylene analogues (-(CH2)(n)-, n = 3-5). From these data. enthalpies of hydration DeltaH degrees (hydr)= DeltaH degrees (sol) - DeltaH degrees (subl) were calculated and corrected for energies of cavity formation in pure liquid water in order to obtain enthalpies of interaction, DeltaH degrees (int) of the solutes with their hydration shells. The latter are discussed together with the recalculated DeltaH degrees (int) for variously methylated uracils, obtained previously according to a simplified correction procedure, in terms of perturbations in the energy and scheme of hydration of the diketopyrimidine ring brought about by alkyl substitution. It was found that each -CH2-group added with an alkyl substitution contributes favorably about -20 kJ mol(-1) toDeltaH degrees (int). This contribution is partially cancelled by the unfavorable contribution to DeltaH degrees (int) connected with removal of some water molecules bound in the first and subsequent hydration layers by an alkyl substituent. This is particularly evident on substitution at the polar side of the diketopyrimidine ring on which water molecules are expected to be bound specifically.

Journal Article↗
PubMed1994

Long-term persistence and cytokinetics of human tumor cells in vitro following high-dose alkylating agent exposure.

Relapse after high-dose alkylating agent therapy continues to be an important clinical issue. To begin to understand the characteristics of cells surviving alkylating agent exposure human MCF-7 breast carcinoma cells were exposed to a range of concentrations of melphalan or cis-diamminedichloroplatinum(II) and cell survival determined by colony formation over a time course of 4 weeks. When antitumor alkylating agent exposure killed 3-4 logs of cells as determined by surviving fraction after 1 week of colony formation a progressive increase in surviving fraction was evident over the 4-week course of the experiment. Many attached single cells with abnormal morphology were evident in these dishes; however, the colonies which arose over the 4-week observation time were made up of cells morphologically indistinguishable from the control cells. Cell cycle patterns in the cultures exposed to high concentrations of the antitumor alkylating agents indicated a block in G2/M but by 4 weeks post-drug exposure most had returned to a normal exponential growth pattern. When MCF-7 cells or human SW2 small cell lung cancer cells were exposed to a concentration of melphalan or cis-diamminedichloroplatinum(II) that killed 1-2 logs of cells followed by exposure to a concentration range of the same drug for 24 h or 7 days later resistance to the second drug exposure was evident in both cell lines. Using [14C]melphalan the uptake of the drug into MCF-7 cells pre-treated was compared. Decreased drug uptake did not appear to be a factor in resistance to melphalan observed upon re-exposure to the drug. The potential clinical implications of these findings is discussed.

Breast Neoplasms↗
PubMed1986

Chemosensitization by monofunctional alkylating agents.

The chemosensitizing ability of model monofunctional alkylating agents with known DNA base alkylating characteristics, that is, methylmethanesulphonate (MMS), ethyl methanesulphonate (EMS) and N-methyl-N-nitrosoguanidine (MNNG) have been investigated. Whereas the alkyl sulphonates chemosensitize V79 cells to cisplatin and melphalan, MNNG does not. The dose response curves show shoulder removal. Drug scheduling and thiourea post-treatment experiments indicate that the effect is likely to be on the initial alkylation rather than completion of crosslink formation from an initial adduct.

Animals↗
PubMed2004

Permeability characteristics and membrane affinity of flavonoids and alkyl gallates in Caco-2 cells and in phospholipid vesicles.

Biomembrane interactions of flavonoids and alkyl gallates were investigated using transport studies on Caco-2 cells and membrane affinity experiments in phospholipid vesicles. Flavone was rapidly absorbed across the cell monolayer (P(app),380 x 10(-6) cm/s), whereas efficient uptake but no apical to basolateral transport was observed with the flavonoids with higher degree of hydroxylation (e.g., quercetin and luteolin). The transport of alkyl gallates was governed by the length of the alkyl chain, i.e., methyl and propyl gallate were absorbed while octyl gallate showed cellular uptake but no transport. Flavonoids with several hydroxyl groups exhibited highest affinity for vesicle membranes, partition coefficients being 7.1 and 7.5 microM for luteolin and quercetin, respectively. In conclusion, the degree of hydroxylation, molecular configuration, and length of the side chain of flavonoids and alkyl gallates seem to have a highly important impact on their membrane affinity as well as on their permeability characteristics in Caco-2 cells.

Absorption↗
PubMed2005

Design and synthesis of alkyl 7,7-dihalo-3-methyl-5-(nitrophenyl)-2-azabicyclo[4.1.0]hept-3-ene-4-carboxylates with calcium channel antagonist activity.

A group of alkyl 7,7-dihalo-3-methyl-5-(2- or 3-nitrophenyl)-2-azabicyclo[4.1.0]hept-3-ene-4-carboxylates were prepared by reaction of dihalocarbenes (:CX(2), X=Br, Cl) with alkyl 2-methyl-4-(2- or 3-nitrophenyl)-1,4-dihydropyridine-3-carboxylates. In vitro calcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle assay. The title compounds exhibited weaker CC antagonist activity (10(-5) to 10(-7)M range) than the reference drug nifedipine (1.4 x 10(-8)M). Structure-activity relationships showed that the position (ortho or meta) of the nitro-substituent on the C-5 phenyl ring, the size (van der Waal's radius for Br and Cl are 1.95 and 1.80A, respectively) and/or electronegativity (Cl>Br) of the C-7 geminal halogen atoms do not appear to have a significant effect on CC antagonist activity. In contrast, the effect of the alkyl ester substituent was more pronounced where compounds having a Me or Et alkyl ester group showed superior potency (IC(50) in the 10(-7)M range) relative to the reference drug nifedipine (IC(50)=1.40 x 10(-8)M). Replacement of a 2-methyl-3-methoxycarbonylvinyl moiety present in nifedipine by a bioisosteric geminal-dihalocyclopropyl moiety provided a novel class of calcium channel antagonists that do not exhibit any inotropic effect on guinea pig atria.

Animals↗
PubMed2005

Anticancer and superoxide scavenging activities of p-alkylaminophenols having various length alkyl chains.

A series of p-alkylaminophenols including 3, p-butylaminophenol; 4, p-hexylaminophenol; 5, p-octylaminophenol; and 6, N-(p-methoxybenzyl)aminophenol were synthesized based on the structure of fenretinide, N-(4-hydroxyphenyl)retinamide (1). This latter agent is a synthetic amide of all-trans-retinoic acid (RA), which is a cancer chemopreventive and antiproliferative agent. It was found that elongation of the alkyl chain length in these compounds increased antioxidative activity and inhibition of lipid peroxidation. These findings led us to investigate whether antiproliferative activity against cancer cells was effected by the length of alkyl chains linked to the aminophenol residue. All p-alkylaminophenols inhibited growth of HL60 and HL60R cells in a dose-dependent manners. The HL60R line is a resistant clone against RA. Growth of various cancer cell lines (HL60, HL60R, MCF-7, MCF-7/Adr(R), HepG2, and DU-145) was suppressed by p-alkylaminophenols in a fashion dependent on the aminophenol alkyl chain length (5>4>3>p-methylaminophenol (2)), with 5 being the most potent inhibitor of cell growth against HL60R, MCF-7/Adr(R), and DU-145 cells among p-alkylaminophenols tested, including 1. In particular, with the exception of compound 2, antiproliferative activity against DU-145 cells by these p-alkylaminophenols was greater than by 1. In HL60 cells, growth inhibition was associated with apoptosis. On the other hand, elongation of the alkyl chain length reduced superoxide trapping capability (2>3>4>5) in contrast to the effects on inhibition of lipid peroxidation. These results indicate that anticancer activity of p-alkylaminophenols correlated with the inhibitory activity of lipid peroxidation, but not with the superoxide scavenging activity.

Aminophenols↗
PubMed2005

Investigation on conformational order and mobility of diamondbond-C18 and C18-alkyl modified silica gels by Fourier transform infrared and solid-state NMR spectroscopy.

The effect of surface coverage and solid supports on the conformational order of alkyl chains of commercially available carbon clad zirconia based supports and synthesised C18-alkyl modified silica based supports are probed in the dry state for the first time using variable temperature Fourier transform infrared (FT-IR) and solid-state 13C NMR spectroscopy. From FT-IR spectroscopy, the conformational order of alkyl chains tethered to the substrates is examined by the analysis of CH2 symmetric and anti-symmetric stretching bands. Through solid-state 13C NMR spectroscopy, the order is inferred from the relative intensity of the main methylene carbon resonance assigned to trans and trans-gauche conformations. It is found that molecules tethered to the graphite layer experience a strongly diamagnetic component of the highly anisotropic magnetic susceptibility of the graphite lattice, which reflects upfield shift in the 13C NMR spectra of commercially available octadecyl-modified carbon clad zirconia based column materials. The present results prove that temperature, surface coverage and solid supports have an influence on the conformational order and mobility of alkyl chains tethered to the carbon clad inorganic metal oxides.

Magnetic Resonance Spectroscopy↗
PubMed2005

Activity and structural changes of mushroom tyrosinase induced by n-alkyl sulfates.

Catecholase activity and structural changes of mushroom tyrosinase (MT) were studied in the presence of some n-alkyl sulfate derivatives. Experiments showed that MT reached its optimal activity in the presence of 1.5, 0.6, and 0.2 mM of sodium n-octyl sulfate (SOS), sodium n-dodecyl sulfate (SDS) and sodium n-tetradecyl sulfate (STS), respectively. Native and incubated MT with the n-alkyl sulfates were also investigated from structural point of view by far-UV circular dichroism (CD) and intrinsic fluorescence spectroscopy. At the above mentioned concentrations of SOS, SDS, and STS no change in the secondary structure of MT was observed. However, changes in the tertiary structure of the enzyme due to the presence of n-alkyl sulfates were obvious. Results of this research indicate that n-alkyl sulfate with longer chain induces greater conformational changes in MT, hence, can activate it at lower concentrations.

Agaricales↗
PubMed2005

Characterization of alkyl phenols in cashew (Anacardium occidentale) products and assay of their antioxidant capacity.

In this study the content of anacardic acids, cardanols and cardols in cashew apple, nut (raw and roasted) and cashew nut shell liquid (CNSL) were analysed. The higher amounts (353.6 g/kg) of the major alkyl phenols, anacardic acids were detected in CNSL followed by cashew fibre 6.1 g/kg) while the lowest (0.65 g/kg) amounts were detected in roasted cashew nut. Cashew apple and fibre contained anacardic acids exclusively, whereas CNSL also contained an abundance of cardanols and cardols. Cashew nut (raw and roasted) also contained low amounts of hydroxy alkyl phenols. Cashew nut shell liquid was used for a basic fractionation of the alkyl phenol classes and the individual anacardic acids, major cardanols and cardols were purified to homogeneity from these fractions by semi-preparative HPLC and definitively identified by nano-ESI-MS-MS, GC-MS and NMR analyses. The hexane extracts (10 mg/ml) of all cashew products tested plus CNSL, displayed significant antioxidant capacity. Cashew nut shell liquid was the more efficient (inhibition=100%) followed by the hexane extract of cashew fibre (94%) and apple (53%). The antioxidant capacity correlated significantly (P<0.05) with the concentration of alkyl phenols in the extracts. A mixture of anacardic acids (10.0 mg/ml) showed the higher antioxidant capacity (IC50=0.60 mM) compared to cardols and cardanols (IC50>4.0 mM). The data shows that of these substances, anacardic-1 was by far the more potent antioxidant (IC50=0.27 mM) compared to cardol-1 (IC50=1.71 mM) and cardanol-1 (IC50>4.0 mM). The antioxidant capacity of anacardic acid-1 is more related to inhibition of superoxide generation (IC50=0.04 mM) and xanthine oxidase (IC50=0.30 mM) than to scavenging of hydroxyl radicals. At present a substantial amount of cashew fibre is mostly used in formulations of animal or poultry feeds. The data presented in this study, indicates that this waste product along with CNSL, both of which contain high contents of anacardic acids, could be better utilized in functional food formulations and may represent a cheap source of cancer chemopreventive agents.

Anacardic Acids↗
PubMed2005

Surface adsorption of zwitterionic surfactants: n-alkyl phosphocholines characterised by surface tensiometry and neutron reflection.

The surface adsorption of n-dodecyl phosphocholine (C12PC) has been characterised by a combined measurement of surface tension and neutron reflectivity. The critical micellar concentration (CMC) was found to be 0.91 mM at 25 degrees C in pure water. At the CMC, the limiting area per molecule (A(cmc)) was found to be 52+/-3 A2 and the surface tension (gamma(cmc)) to be ca. 40.0+/-0.5 mN/m. The parallel study of chain isomer n-hexadecyl phosphocholine (C16PC) showed a decrease of the CMC to 0.012 mM and a drop of gamma(cmc) to 38.1+/-0.5 mN/m. However, A(cmc) for C16PC was found to be 54+/-3 A2, showing that increase in alkyl chain length by four methylene groups has little effect on A(cmc). The almost constant A(cmc) suggested that the limiting area per molecule was determined by the bulky PC head group. It was further found that the surface tension and related key physical parameters did not vary much with temperature, salt addition, solution pH or any combination of these, thus showing that surface adsorption and solution aggregation from PC surfactants is largely similar to the zwitterionic betaine surfactants and is distinctly different from ionic and non-ionic surfactants. The thickness of the adsorbed monolayers measured from both dC12hPC and dC16hPC was found to be 20-22 A at the CMC from neutron reflectivity. Neither A(cmc) nor layer thickness varied with alkyl chain length, indicating that as the alkyl chain length became longer it was further tilted away from the surface normal direction and the layer packing density increased. It was also observed that the thickness of the layer varied little with surfactant concentration, indicating that the average conformational orientation of the alkyl chain remained unchanged against varying surface coverage.

Adsorption↗
PubMed2006

Quantitative structure and retention relationships for gas chromatographic data: application to alkyl pyridines on apolar and polar phases.

Quantitative structure and retention relationships (QSRR) have been developed to model gas chromatographic retention data of alkyl pyridines on apolar (branched alkane) and polar (primary alcohol) stationary phases. The retention properties analyzed are Kovats retention index, I; partial molar enthalpy, DeltaH; partial molar entropy, DeltaS and partition coefficient, log K. Using the seven valence molecular connectivity indices (chi) calculated for the 18 alkyl pyridines, regression models are generated to predict the retention properties. The best model (model A) obtained with the descriptors ((1)chi(P)(V), (3)chi(P)(V) and (6)chi(CH)(V) was unable to produce a satisfactory statistical performance and correct order of elution. The model has been modified (model B) by including steric parameter s, which has been empirically derived by considering the steric effects due to the presence of alkyl groups at the ortho and meta positions. The modified model predicts the correct order of elution for all the alkyl pyridines and good correlation coefficients, r. The r values obtained for I, DeltaH, DeltaS and log K are: r=0.955, 0.975, 0.984 and 0.955 (model A) become r=0.999, 0.996, 0.990 and 0.999 (model B) on the apolar stationary phase and r=0.931, 0.926, 0.911 and 0.931 (model A) become r=0.999, 0.992, 0.958 and 0.999 (model B) on the polar stationary phase.

Chromatography, Gas↗
PubMed2005

4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes.

4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-alkyl-HIBO analogues have been extended in this paper in the search for versatile agents. Pharmacological characterization of five new analogues, branched and unbranched 4-alkyl-HIBO analogues, have been carried out. The present compounds are all weak antagonists at Group I mGluRs (mGluR1 and 5) presenting only small differences in potencies (Ki values ranging from 89 to 670 microM). Affinities were studied at native and cloned iGluRs, and the compounds described show preference for the AMPA receptor subtypes GluR1 and 2 over GluR3 and 4. However, compared to previous 4-alkyl-HIBO analogues, these compounds show a remarkably high affinity for the Kain preferring subtype GluR5. The observed GluR5 affinities were either similar or higher compared to their GluR1 and 2 affinity. Isopropyl-HIBO showed the highest affinity for GluR5 (Ki=0.16 microM), and represents a unique compound with high affinity towards the three subtypes GluR1, 2 and 5. In general, these compounds represent new selectivity profiles compared to previously reported Glu receptor analogues.

Animals↗
PubMed2000

Acceleration of phospholipid flip-flop in the erythrocyte membrane by detergents differing in polar head group and alkyl chain length.

The detergents, alkyltrimethylammonium bromide, N-alkyl-N, N-dimethyl-3-ammonio-1-propanesulfonate (zwittergent), alkane sulfonate, alkylsulfate, alkyl-beta-D-glucopyranoside, alkyl-beta-D-maltoside, dodecanoyl-N-methylglucamide, polyethylene glycol monoalkyl ether and Triton X-100, all produce a concentration-dependent acceleration of the slow passive transbilayer movement of NBD-labeled phosphatidylcholine in the human erythrocyte membrane. Above a threshold concentration, which was well below the CMC and characteristic for each detergent, the flip rate increases exponentially upon an increase of the detergent concentration in the medium. The detergent-induced flip correlates with reported membrane-expanding effects of the detergents at antihemolytic concentrations. From the dependence of the detergent concentration required for a defined flip acceleration on the estimated membrane volume, membrane/water partition coefficients for the detergents could be determined and effective detergent concentrations in the membrane calculated. The effective membrane concentrations are similar for most types of detergents but are 10-fold lower for octaethylene glycol monoalkyl ether and Triton X-100. The effectiveness of a given type of detergent is rather independent of its alkyl chain length. Since detergents do not reduce the high temperature dependence of the flip process the detergent-induced flip is proposed to be due to an enhanced probability of formation of transient hydrophobic structural defects in the membrane barrier which may result from perturbation of the interfacial region of the bilayer by inserted detergent molecules.

4-Chloro-7-nitrobenzofurazan↗
PubMed1996

Differential effect of alkyl chain-modified ether lipids on protein kinase C autophosphorylation and histone phosphorylation.

Analogues of 1-O-octadecyl-2-O-methyl-rac-glycerol-3-phosphocholine (ET-18-OMe), containing a carbonyl group at different positions in the alkyl chain and/or a pentylammonium group in sn-3 of glycerol, were evaluated as inhibitors of protein kinase C (PKC; EC 2.7.1.37). The presence of a carbonyl group in the alkyl chain of Et-18-OMe had a dual role in decreasing the inhibitory effect on histone phosphorylation and activating this reaction at low concentrations of compound. The optimal stimulatory effect was observed with the compound having the carbonyl function in C-7 of the alkyl chain. In contrast, all of these compounds were only inhibitors of PKC autophosphorylation, its potency decreasing progressively with the distance between the carbonyl group and the sn-1 position of glycerol. Replacement of the phosphocholine group of ET-18-OMe by a pentamethylene trimethylammonium group maintained the inhibitory effect on histone phosphorylation and autophosphorylation of PKC, and the simultaneous introduction of a ketone group in C-7 of the alkyl chain did not decrease any of these effects. The effects of all these analogues on PKC autophosphorylation, but not on histone phosphorylation, correlated quite well with their known antiproliferative activity on human tumor cell lines and membranolytic activity.

Animals↗
PubMed2004

Protective role of aryl and alkyl diselenides on lipid peroxidation.

The concept that selenium-containing molecules may be better nucleophiles (and therefore antioxidants) than classical antioxidants has led to the design of synthetic organoselenium compounds. In the present study we appraised the antioxidant potential, thiol peroxidase activity, and rate of dithiotreitol and reduced glutathione oxidation of simple organodiselenide compounds in rats and mice. The present results demonstrate that alkyl and aryl diselenides are antioxidant compounds. We verified that the substitution on the aromatic moiety of diphenyl diselenide or the replacement of on aryl group by an alkyl substitute on diselenides changes their antioxidant and thiol peroxidase-like properties. The diaryl diselenides (PhSe)(2) and (p-ClPhSe)(2) presented higher thiol peroxidase activity and demonstrated better antioxidant potential than the other diselenides tested. In fact, the results revealed that alkyl diselenides, at low concentrations, were prooxidants and that aryl diselenides did not present this effect. Alkyl diselenides [(C(2)H(5)Se)(2) and (C(3)H(7)Se)(2)] demonstrated a higher potential for -SH group oxidation than aryl diselenides. In addition, this study demonstrated that diselenide protection against lipid peroxidation was different in mice and rats. The compounds tested acted more as antioxidants in the brains of mice than in the brains of rats.

Animals↗