N-ethyl Groups Research Articles

Synthesis of Indolyl Pyrazole Scaffolds as Potential Anti-cancer Agents and their Molecular Modelling Studies

Background:: Indole and pyrazoles are one of the prime structural units in the field of medicinal chemistry and have been reported to exhibit a variety of biological activities specifically anti-cancer. In view of their medicinal significance, we synthesized a conjugate of the two moieties to get access to newer and potential anti-cancer agents. Methods: Indolyl pyrazoles [3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-indole-3-carbon yl)acrylonitriles] (4a-l) were synthesized by adopting simple and greener protocol and all the synthesized derivatives were docked against Bcl-2 protein and the selected chemical moieties were screened for their cytotoxicity by using the MTT assay. Results: : All the synthesized compounds were docked against BCL-2 protein in order to understand their binding pattern. Among the 12 compounds docked, 4d, 4f, 4h, 4j, and 4l compounds exhibited better protein binding interactions and the same were screened for their anti-cancer activity against A549 (lung) cancer cell lines at a concentration of 100 μM using Doxorubicin as standard. Substitutions such as N-benzyl, N-ethyl groups and halogen groups such as Br, Cl on indole ring showed moderate activity against A-549 cell lines. Conclusion:: Among the 5 indolyl pyrazole derivatives screened, compounds 4h and 4j showed significantly better activity with an IC50 of 33.12 and 34.24 μM, respectively. Further, structural tweaking of the synthesized new chemical entities may lead to potential hit/lead-like molecules.

Synthesis and dyeing properties of indophenine dyes for polyester fabrics

In this study, a series of indophenine dyes (D1-D6) that show high molecular planarity, were synthesized and applied as dyeing materials for poly (ethylene terephthalate) fabrics. The relationship between the dye molecular structure and dyeing properties, such as dyeing rate and color fastness properties, was investigated. Compared with conventional azo or anthraquinone dyes, the indophenine dyes had a much lower dyeing rate but very good anti-thermomigration properties. This phenomenon indicated that there exists much larger intermolecular interaction between indophenine dye molecules, which was also confirmed by the results of quantum chemical density functional theory (DFT) calculations. The substituent effect of alkyl groups and halogen atoms (F and Cl) was also investigated. The steric hindrance of linked ethyl groups could efficiently promote dyeing performance, while halogen atoms lowered the color acquisition. As a result, D4 with only two N-ethyl groups incorporated on the indophenine backbone showed the best overall dyeing performance.

Study of the effect of thiourea and N-ethyl groups on antibacterial activity of rhodamine-labeled 3,4-HPO iron chelators against Gram (+/−) bacteria

In the sequence of the work in which we identified functional groups of rhodamine labeled 3,4-HPO chelators that are crucial for their activity against Mycobacterium avium infection we now scrutinize if the same groups are also relevant for the chelators antibacterial activity against Gram (+/−) bacteria. In this new infection scenario, we confirmed that a thiourea linkage and N-ethyl substituents on the xanthene ring are important and there is an advantage of the association of both groups in the molecular framework. In particular, we found that three hexadentate chelators (MRH7, MRH8, and MRH10) inhibit bacterial growth of Staphylococcus (S). aureus ATCC 25923 and S. epidermis ATCC 12228 and one hexadentate chelator (MRH7) also inhibits the growth of Escherichia (E.) coli ATCC 25922.

Tuning photophysical properties and electronic energy levels of 1-aminoanthraquinone derivatives by introducing N-ethyl substituent

It is proved that introducing the ethyl substituted group to 1-amino will enhance the intramolecular charge transfer (ICT) process of 1-N substituted anthraquinone derivatives. Bathochromic shift of the absorption maxima and diminished absorption intensity are observed with the increase of the electron donation abilities of the N-ethyl groups. Moreover, the intramolecular and intermolecular hydrogen bonds further intensify the ICT properties through introducing the end amino group. This work exhibits more effective acceptors than anthraquinone in novel multichromophore materials for organic solar cells and other optoelectronic devices.

Synthesis and X-ray analysis of a perfluoroalkyl-substituted azobenzene dye

A search for colorants capable of reducing the surface energy of synthetic fibers as well as adding color led to the synthesis and characterization of the repellency behavior of dyes such as 4-N,N-diethylamino-4′-tridecafluorohexylazobenzene. Unexpectedly high surface energy values and a low fluorine content on fiber surfaces then led to an interest in determining the crystal structure of this new dye. Accordingly, a single crystal was grown from acetone solution, and its structure was established using X-ray diffraction analysis. Interestingly, it was found that the azobenzene skeleton is appreciably nonplanar, having an N2–N1–C1–C2 torsion angle of 30.6°, despite the absence of substituents ortho to the azo bond. Further, the structure is characterized by head-to-tail molecular stacking and the N-ethyl groups in the molecule are positioned above the aminobenzene plane on the same side. It is likely that this combination of factors contribute to the observed surface properties of the target dye.

Photoinduced electron transfer in rhodamine B-containing amorphous titania gels

Amorphous titania gel films containing the dye rhodamine B (RhB) were prepared by a sol–gel method, without heating. The RhB existed in the films as the RhB cation, which was transformed into the rhodamine 110 (Rh110) cation; its xanthene skeleton then decomposed during irradiation with visible light. This process was induced by electron transfer from the RhB cation to the titania gel matrix, because formation of the RhB radical on loss of an electron caused sequential dissociation of the N-ethyl groups. During irradiation with visible light a photocurrent was observed in electrodes coated with the RhB-containing titania gel and immersed in an I2–LiI electrolyte. This photocurrent resulted from electron injection from the LUMO level of the dye into conduction band-like states of the titania gel. Because of its effective electron supply the electrolyte inhibited dissociation of the N-ethyl groups of RhB.

Thermoresponsive fluorinated polyacrylamides with low cytotoxicity

We report the unique thermoresponsive properties of fluorinated polyacrylamides, poly[N-(2,2-difluoroethyl)acrylamide] (P2F). The solubility of fluorinated polyacrylamides in water can be easily controlled by changing the number of fluorine atoms in N-ethyl groups. Moreover, we demonstrate that fluorinated polyacrylamides are less cytotoxic than poly(N-isopropylacrylamide) (PNIPAM).

Non-conjugated dendrimers with a porphyrin core and coumarin chromophores as peripheral units: Synthesis and photophysical properties

Three porphyrin-cored dendrimers with non-conjugated coumarins as dendrons have been synthesized and characterized. The photophysical properties of the title compounds were investigated by means of UV/Vis absorption and fluorescence spectroscopy in dilute CH 2Cl 2 solutions and in thin neat films. The intramolecular energy transfer from the coumarin units to the porphyrin core clearly reveals two factors influencing energy-transfer efficiency. Firstly, a better spectral overlap between the absorption spectrum of porphyrin core and the emission spectrum of the coumarin moiety results in high energy-transfer efficiency. Secondly, a long alkyl side-chain improves solubility of dendrimers, but also prevents the coumarins from self-quenching. Hence, the dendrimer with N-octyl groups possesses a higher efficiency than that with N-ethyl groups. The dendrimers emit red light with higher fluorescence quantum yields over the free porphyrin.

Determination of the binding epitope of lidocaine with AGP: minimizing the effects of nonspecific binding in saturation transfer difference experiments

The ligand epitope map and the effect of nonspecific binding is assessed for lidocaine binding to α(1)-acid glycoprotein using the saturation transfer difference nuclear magnetic resonance experiment performed as a function of the ligand/protein ratio. The experimental design tested two different approaches for preparing solutions with various ligand/protein ratios; holding the protein concentration constant and increasing the ligand concentration; and holding the ligand concentration constant while decreasing the protein concentration. Nonspecific binding effects were more prevalent in experiments in which the ligand concentration was increased, although spectra with higher signal-to-noise ratios were obtained under these conditions. The epitope map determined for achiral lidocaine is compared with previously determined results for the (R)- and (S)-enantiomers of propranolol. The weaker binding affinity of lidocaine may be partially attributed to steric hindrance by the lidocaine N-ethyl groups which may prevent close contact of the lidocaine amine with the negatively charged amino acids at the apex of the protein binding pocket.

X-ray structures and computational studies of several cathinones

2-(Ethylamino)-1-(4-methylphenyl)propan-1-one (shortly named 4-MEC) ( 1a), 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (shortly named methylone or 3,4-methylenedioxymethcathinone) ( 1b), 1-(3,4-dimethylphenyl)-2-(methylamino)propan-1-one ( 1c), 2-methylamino-1-(4-methylphenyl)propan-1-one (shortly named mephedrone; 4-MMC or 4-methylmethcathinone) ( 1d) and 2-(methylamino)-1-phenylbutan-1-one (shortly named buphedrone) ( 1e) and their aminium salts ( 2a–e), are examples of cathinones which were characterized by FTIR, UV–Vis, multinuclear NMR spectroscopy. By single crystal X-ray diffraction method structures of 2a, 2b, 2c and 2d were determined. NMR solution spectra showed readily diagnostic H-1 and C-13 signals from methyl, ethyl, N-methyl or N-ethyl groups. The diastereotopic methylene protons of 1a appear as an ABX 3, and 1e and 2e appear as an ABMX 3 system. The geometries of the studied compounds were optimized in singlet states using the density functional theory (DFT) method with B3LYP functional. Electronic spectra were calculated by TDDFT method. In general, the predicted bond lengths and angles are in good agreement with the values based on the X-ray crystal structure data.

The remarkable effect of 7-amino substituents on the reactivity of 4-nitrobenzofurazans with nucleophiles

The reactions of four 4-nitrobenzofurazans (4a–4d) substituted at the 7 position with (a) N-ethyl, (b) N-butyl, (c) piperidino, or (d) pyrrolidino groups have been examined with sulfite ions and with hydroxide ions in water–DMSO (80:20, v/v). Addition of sulfite at the 5 position gives σ adducts with equilibrium constants ca. 105lower than that for the formation of the corresponding adduct from 4-nitrobenzofurazan. These reductions are attributed to the stabilization of the parent molecules 4a–4d by conjugative interaction between the 4 and 7 substituents. In alkaline solution, 4a and 4b yield the conjugate bases while 4c and 4d suffer nucleophilic substitution to give 7-hydroxy-4-nitrobenzofurazan. Reactivity here is relatively high because of the iminium ion character of the substrates. Key words: benzofurazans, σ adducts, nucleophilic reactivity, substitution.

Formation and identification of intermediates in the visible-light-assisted photodegradation of sulforhodamine-B dye in aqueous TiO2 dispersion.

The photodegradation of dye pollutants under visible light irradiation in TiO2 dispersions continues to draw considerable attention because of the greater effective utilization of solar energy and its potential application in treating wastewaters from textile and photographic industries. To get a better handle on the mechanistics details of this TiO2-assisted photodegradation of dyes with visible radiation, the process was examined by UV-visible spectroscopy, high-performance liquid chromatography, silica gel thin-layer chromatography, and matrix-assisted laser desorption ionization time-of-flight mass spectrometric techniques to separate and identify the N-de-ethylated intermediate products during the photodegradation of N,N,N,N-tetraethylsulforhodamine-B (SRB) in the absence and presence of iodide ions. Five intermediates, namely, N,N-diethyl-N'-ethyl-sulforhodamine, N,N-diethylsulforhodamine, N-ethyl-N'-ethylsulforhodamine, N-ethylsulforhodamine, and sulforhodamine were thus identified. They correspond to intermediate products having a different number of N-ethyl groups, which are removed sequentially from the SRB molecule. The reaction process was accompanied by the oxidation of I- to I3- in the presence of I- ions. Formation of radicals was assessed by spin-trap electron spin resonance spectrometry. The experimental results provided the basis for a more detailed description of the reaction mechanism(s).

New Intermediates of Dealkylation of [ 14C]Atrazine by Mouse Liver Microsomes

The metabolism of 50 μ M [2,4,6- 14C]atrazine by liver microsomes from ICR strain mice produced metabolites not previously described which account for about 25% of total transformation products, plus 10-14% deethylatrazine and 13-15% deisopropylatrazine, based on the total radioactivity injected into an analytical high-pressure liquid chromatography (HPLC) system. The unknown metabolites were observed by HPLC of products from atrazine incubations with liver microsomes from both untreated mice and mice treated with phenobarbital. Two major unidentified peaks (Unknowns 1 and 2) were isolated and collected by HPLC and characterized by gas chromatography-electron-impact ionization-mass spectrometry. Unknown 1 was an unstable intermediate, likely a mixture of carbinolamines, that decomposed into deethylatrazine, and Unknown 2, a mixture of compounds unseparated by HPLC probably with N-vinyl substituents at the location of the N-isopropyl and N-ethyl groups of the atrazine molecule with M + at m/ z 213. While microsomal oxidation did produce a mixture of trace amounts of breakdown products of atrazine, the method was impractical for the initial goal of preparing pure dealkylated atrazine derivatives for environmental degradation studies.

The electrostatic contribution to binding in the choline transport system of erythrocytes.

Half-saturation constants have been determined for the choline carrier with cationic substrates and their uncharged carbon analogs: (a) choline and 3,3-dimethyl-1-butanol and (b) 2-dimethylaminoethanol and isoamyl alcohol. The constants are 6.3 microM and 16 mM for the first pair, and 19 microM and 45mM for the second. In both cases, the charged molecules have the higher affinity by a factor of more than 2000. This is to be compared with a factor of less than 10 for charged and neutral substrates of acetylcholinesterase, and with a similar factor in antigen-antibody reactions. To account for the unusually strong ionic bond, a very close association between the carrier site and the substrate is suggested, probably with exclusion of water of hydration. This is supported by the fact that gradual replacement of N-methyl groups in the substrate by N-ethyl groups sharply reduces affinity for the carrier with a 110-fold reduction overall, but has no significant effect on the enzymes.

The structure of karakolidine

As the result of a study of chemical transformations and spectral characteristics, for the new alkaloid karakolidine a lycoctonine skeleton with N-ethyl and C4-methyl groups, hydroxy groups at C1 (α), C8, C10 (α), and C13, and a methoxy group at C15 (β) has been established.

Purification and properties of the trimethylamine dehydrogenase of bacterium 4B6.

1. The trimethylamine dehydrogenase of bacterium 4B6 was purified to homogeneity as judged by analytical polyacrylamide-gel electrophoresis. The specific activity of the purified enzyme is 30-fold higher than that of crude sonic extracts. 2. The molecular weight of the enzyme is 161000. 3. The kinetic properties of the purified enzyme were studied by using an anaerobic spectrophotometric assay method allowing the determination of trimethylamine dehydrogenase activity at pH8.5, the optimum pH. The apparent K(m) for trimethylamine is 2.0+/-0.3mum and the apparent K(m) for the primary hydrogen acceptor, phenazine methosulphate, is 1.25mm. 4. Of 13 hydrogen acceptors tested, only Brilliant Cresyl Blue and Methylene Blue replace phenazine methosulphate. 5. A number of secondary and tertiary amines with N-methyl and/or N-ethyl groups are oxidized by the purified enzyme; primary amines and quaternary ammonium salts are not oxidized. Of the compounds that are oxidized by the purified enzyme, only trimethylamine and ethyldimethylamine support the growth of bacterium 4B6. 6. Trimethylamine dehydrogenase catalyses the anaerobic oxidative N-demethylation of trimethylamine with the formation of stoicheiometric amounts of dimethylamine and formaldehyde. Ethyldimethylamine is also oxidatively N-demethylated yielding ethylmethylamine and formaldehyde; diethylamine is oxidatively N-de-ethylated. 7. The activity of the purified enzyme is unaffected by chelating agents and carbonyl reagents, but is inhibited by some thiol-binding reagents and by Cu(2+), Co(2+), Ni(2+), Ag(+) and Hg(2+). Trimethylamine dehydrogenase activity is potently inhibited by trimethylsulphonium chloride, by tetramethylammonium chloride and other quaternary ammonium salts, and by monoamine oxidase inhibitors of the substituted hydrazine and the non-hydrazine types. 8. Inhibition by the substituted hydrazines is time-dependent, is prevented by the presence of trimethylamine or trimethylamine analogues and in some cases requires the presence of the hydrogen acceptor phenazine methosulphate. The inhibition was irreversible with the four substituted hydrazines that were tested.

The Stereochemistry of the Quaternization of 5-Methyl-5-nitro-1, 3-dialkylhexahydropyrimidines

The proportions of isomers existing in the quaternization products were estimated from the nuclear magnetic resonance (NMR) and thin-layer chromatography data. Based on those data, the stereoselectivity of the quaternization of some 5-methyl-5-nitro-1, 3-dialkylhexahydropyrimidines with alkyl iodide was discussed. NMR characteristics and particularly the chemical shifts of axial and equatorial N-methyl and N-ethyl groups were used to assign the configurations.

The conformational analysis of saturated heterocycles. Part XXIII. Hexahydropyrimidines

The preparations of some N-substituted hexahydropyrimidines are described. Their electric dipole moments have been measured in cyclohexane solution and interpreted in terms of their conformations. The conformational free-energy differences between axial and equatorial N-methyl and N-ethyl groups are a little smaller than in the corresponding N-alkylpiperidines and accord with a repulsion between two axial lone electron pairs of about 0·3 kcal./mole. For N-isopropyl groups the conformational free-energy difference is surprisingly high; a possible explanation is suggested.

The conformational analysis of saturated heterocycles. Part XII. Conformations of 1-alkyl-4-t-butylpiperazines from electric dipole moment studies

An improved technique for the measurement of electric dipole moments is described. The dipole moments of 1-alkyl-4-t-butylpiperazines indicate that the axial–equatorial conformational equilibria for N-methyl and N-ethyl groups is predominantly in favour of the conformer with axial lone pair and equatorial alkyl group.

Applications of pyrohydrolytic cleavages in spot test analysis A contribution to the chemistry of specific, selective and sensitive reactions

Abstract If organic compounds are heated in contact with hydrates of naanganous sulphate or oxalic acid or if they are heated along with succinic or phathlic acid, the water released in the temperature range 100–230° can accomplish hydrolyses that do not occur with boiling water. The term pyrohydrolysis is suggested for those hydrolyses which can be accomplished only at elevated temperatures. Analytical applications of pyrohydrolyses are possible provided brief heating with appropriate water donors yields cleavage products which can be readily detected in the gas phase. Examples are given of the detection of: heliein by splitting off salieylaldehyde; anilides of aliphatic carboxylic acids by splitting off aniline; O-acetyl compounds by evolution of acetic acid; aliphatic-bound halogen by splitting off hydrogen halides; aromatic sulphonic acids by generation of sulphur dioxide; N-methyl and N-ethyl groups by production of formaldehyde and acetaldehyde respectively. All of the tests can be successfully conducted within the bounds of spot test analysis and possess microanalytical limits of detection.