N-methyl Carbazole Research Articles

Discovery of novel N-methyl carbazole tethered rhodanine derivatives as direct inhibitors of Mycobacterium tuberculosis InhA.

InhA (Enoyl-ACP reductase) plays a crucial role in the biosynthetic pathway of cell wall synthesis in Mycobacterium tuberculosis (Mtb). Isoniazid (INH) is an important first-line drug, which inhibits InhA. The rapid increase in resistance to INH and currently marketed drugs as well as emergence of MDR-TB and XDR-TB has complicated the diagnosis and treatment of Mtb with ever increasing threat to human kind. Herein, we report novel N-methyl carbazole derivatives as potential anti-TB compounds acting directly via InhA inhibition. All the synthesized final compounds were screened against Mtb virulent cell line H37Rv and investigated the InhA enzyme inhibition. Interestingly, compound 9e displayed promising inhibition (91%) at 50 µM concentration and IC50 of 2.82 µM against InhA. To understand the ligand receptor interaction between compound 9e and InhA, molecular docking and molecular dynamics experiments were performed. The computational results were in agreement with the observed experimental data. Further, the cytotoxicity studies on mammalian cells revealed that all the compounds were safe.

Dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2-aminothiazoles and their cinnamamides as potent inhibitors of Mycobacterium tuberculosis

Herein described the design, synthesis and antitubercular evaluation of novel series of dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2-aminothiazoles and their cinnamamide analogs. One pot condensation of N-methyl carbazole, dibenzofuran and dibenzothiophene methyl ketones with thiourea in the presence of Iodine and CuO gave respective 2-aminothiazoles 4–6 in very good yields. Aminothiazoles were further coupled with substituted cinnamic acids using acid-amine coupling conditions to give desired cinnamamide analogs 8a–e, 9a–e and 10a–e. All the newly synthesized compounds were fully characterized by their NMR and mass spectral analysis. In vitro screening of new derivatives against Mycobacterium tuberculosis H37Rv (Mtb) resulted 8c, 10d and 10e (MIC: 0.78 µg/mL) and 2-aminothiazoles 5 and 6 (MIC: 1.56 µg/mL) as potent compounds with lower cytotoxicity profile.

Inhibition of steel corrosion by potentiodynamic deposition of poly(N-methyl carbazole)

Poly(N-methyl carbazole) (PNMeCz) coating was deposited on 304 type stainless steel (SS) by electropolymerization of N-methyl carbazole monomer in tetrabutylammonium perchlorate containing acetonitrile solution using cyclic voltammetry. PNMeCz coating was characterized by attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy, thickness, conductivity, and contact angle measurements. Corrosion performance of the polymer-coated steel electrodes was investigated in 1 M H2SO4 solution using open circuit potential–time (Eocp–t) curves, potentiodynamic polarization, and electrochemical impedance spectroscopy techniques. PNMeCz coating was found to provide anodic protection to the substrate and significantly reduce the corrosion rate of SS in acidic medium.

High contrast solid-state electrochromic devices from substituted 3,4-propylenedioxythiophenes using the dual conjugated polymer approach

Solid-state electrochromic windows from 3,4-propylenedioxythiophene (ProDOT) derivatives using dual polymer electrochromic architecture were fabricated and their electro-optical characteristics were recorded. DibenzylProDOT (DiBz-ProDOT) and biphenylmethyloxymethyl ProDOT (BPMOM-ProDOT) were used as cathodically coloring polymers, whereas bis(2-(3,4-ethylenedioxy)thienyl)- N-methyl carbazole (BEDOT-NMCz) was used as their complementary anodically coloring polymer. Straightforward assembly of the devices was designed by means of using a UV photo-curable gel. These devices exhibited response speeds of approximately 1 s with photopic contrasts as high as 52% for the complete device, and were found to exhibit good stability under open circuit conditions. Convenience of reporting photopic values to characterize electrochromic devices compared to reporting contrasts at a single wavelength is remarked.

Experimental determination of the solvation shifts of purely electronic spectra and their Franck-Condon components

The possibilities of using resonance spectra to determine the solvation shifts of purely electronic bands of organic luminophores in solutions and the contributions to these shifts from Franck-Condon components arising due to relaxation of solvation shells are discussed. It is shown that, upon a change in the solvation conditions, the relaxation processes accompanying the purely electronic transition of organic luminophores in solutions can significantly contribute to the solvation shifts of absorption and luminescence bands. Therefore, for the spectroscopic analysis of intermolecular interactions in solutions to be correct, the contribution from the Franck-Condon components should be quantitatively taken into account. Using carbazole and N-methyl carbazole as an example of luminophores with identical chromophore nuclei, it is found that intermolecular hydrogen bonds do not manifest themselves in the relaxation of the solvation environment, while the contribution from intermolecular interactions of a universal (van der Waals) character to the solvation shifts of such systems is the same.

Metabolism of N-methylcarbazole by rat lung microsomes.

N-methylcarbazole (NMC) is a procarcinogenic component of tobacco smoke particulate matter. It is metabolized by liver microsomes into some hydroxylated metabolites such as the potent mutagen N-hydroxymethylcarbazole (NHMC). Lung metabolism and toxicity of NMC is not known. Since the lung is the primary organ of inhalation of tobacco smoke, NMC metabolism by lung microsomes was studied in comparison with the metabolism by liver microsomes. Liver or lung microsomes (1 mg/mL) were incubated with 0.5 mM NMC for 30 min at 37 degrees C. NMC metabolites were extracted with ethyl acetate and analyzed by reversed-phase high-performance liquid chromatography. Rat lung microsomes metabolized NMC with a similar profile to liver microsomes, although lung microsomes produced greater number of metabolites. The potent mutagen NHMC was also the major NMC metabolite produced by lung microsomes, as confirmed by particle beam mass spectrometry. However, lung microsomes produced only 10% of NHMC produced by liver microsomes. Metabolism of NMC by lung microsomes also led to depletion of the endogenous antioxidant glutathione by 34% compared to controls, indicating a significant generation of some reactive intermediates during NMC metabolism by lung microsomes. The data show that the lung participates directly in producing the potent mutagen NHMC from NMC present in tobacco smoke.

Microbial models of mammalian metabolism: involvement of cytochrome P450 in the N-demethylation of N-methylcarbazole by Cunninghamella echinulata.

1. As previously reported (Yang and Davis 1992), N-methylcarbazole (NMC) is converted to N-hydroxymethylcarbazole (NHMC), and 3-hydroxy-N-hydroxymethylcarbazole (3-OH-NHMC), two relatively stable carbinolamine metabolites by the fungus Cunninghamella echinulata (ATCC 9244). Decomposition of these two carbinolamines yields the corresponding dealkylated metabolites, carbazole and 3-hydroxycarbazole. In the present study, the possible involvement of cytochrome P450 in the requisite N-alkyl hydroxylation reaction was examined. 2. Carbon monoxide, a classical P450 inhibitor, markedly inhibited the formation of NHMC, as did potassium cyanide. 1-Benzylimidazole, piperonyl butoxide and SKF-525A inhibited the formation of both NHMC and 3-OH-NHMC, while beta-naphthoflavone (5,6-benzoflavone) induced their formation. 3. The source of the oxygen atom in the metabolite NHMC was examined by GC/MS analysis of NHMC formed during incubation of NMC in H218O-enriched medium which resulted in no incorporation of labelled oxygen into the metabolite. 4. An intermolecular isotope effect was not observed for the formation of NHMC suggesting that C-H bond cleavage is not a rate limiting step in the formation of this metabolite under the conditions examined. 5. It was concluded that P450 enzymes may be involved in the N-demethylation of NMC catalyzed by this fungal model of mammalian metabolism, and provides further support for biochemical and mechanistic parallels between mammalian metabolism and microbial systems catalyzing phase-1 biotransformations.

Synthesis and thermal stability, dielectric, and conductivity characteristics of some carbazole‐bearing pendant and backbone sulfones

AbstractA group of poly(N‐vinylcarbazole) pendant polysulfones has been prepared by reacting it with benzene, toluene, p‐chlorobenzene‐ and p‐nitrobenzenesulfonyl chloride and N‐methyl carbazole, 3,6‐disulfonyl chloride by the Friedel Crafts reaction. Carbazole‐based backbone polysulfones have also been prepared by the reaction of N‐methyl carbazole, 3,6‐disulfonyl chloride and biphenyl, naphthalene, anthracene, and carbazole in presence of anhydrous aluminum chloride. The various sulfone polymers, thus prepared, have been structurally characterized by elemental analysis and IR spectroscopy. Detailed analyses of thermal stability, dielectric, and conductivity characteristics have revealed certain significant differences between these two types of sulfone polymers.

Production of a toxic, novel mammalian metabolite of N-methylcarbazole predicted by a fungal cell model of mammalian metabolism

The formation of N-hydroxymethylcarbazole (NHMC), carbazole, 1-hydroxy- N-methylcarbazole, 2-hydroxy- N-methylcarbazole, and 3-hydroxy- N-methylcarbazole as products of mammalian liver microsomal metabolism of N-methylcarbazole (NMC) has been documented by several investigators. In previous studies in our laboratory, the fungus Cunninghamella echinulata (ATCC 9244) produced two new metabolites, 3-hydroxy- N-hydroxymethylcarbazole (3-OH-NHMC), and 3-hydroxycarbazole (3-OH-carbazole), in addition to the known mammalian metabolites, NHMC and carbazole. One of the two novel metabolites isolated from the microbial models, 3-OH-NHMC, was also identified and characterized in rat liver microsomes by analytical (HPLC) and spectral (UV and NMR) comparisons with a reference standard. The two metabolites, 3-OH-NHMC and 3-OH-carbazole, were shown to be cytotoxic to cultured rat hepatocytes as assessed by lactate dehydrogenase (LDH) leakage and neutral red (NR) uptake. These studies demonstrate the prospective potential of microbial models for predicting the formation of metabolites from drugs and other xenobiotics in mammalian systems.

Studies on the photophysical properties of some 2,7- dimethoxycarbazoles in various environments by steady state and time resolved spectroscopic methods Part 1. Synthesis, absorption and fluorescence spectra at room temperature

The electronic spectroscopic and photophysical properties of 2,7-dimethoxy- N-methyl carbazole (DMNMC) and 2,7-dimethoxycarbazole (DMC) in various polar and non-polar environments at room temperature were compared with those of N-methylcarbazole (NMC). The synthesis and characterization of these compounds are described. The first two electronic transitions 1L b ← 1A and 1L a ← 1A which are well separated and characterized in NMC and carbazole are mixed in the absorption and fluorescence spectra of DMNMC and DMC. This “proximity effect” is responsible for the unidentified first absorption band system observed in solvents at room temperature, for a marked decrease in both the fluorescence quantum yields and lifetimes (NMC, τ F = 15.1 ns; DMNMC, τ F = 8.4 ns; DMC, τ F = 3.9 ns in 3-methylpentane) and for a loss of the mirror-image between the absorption and the fluorescence spectra of these dimethoxy derivatives. The importance of the vibronic interactions between these two states is shown to be controlled (reduced) by N-methylation and/or the intermolecular hydrogen bonding formation in a proton-acceptor solvent such as ethanol.

Polycondensation of N-methyl carbazole with dihalogenomethane and some properties of the polymer

N-methyl carbazole was reacted with dichloromethane or dibromomethane in the presence of AlCl3,SbCl5 or SnCl4 to give a polymer. In several cases insoluble structures with semiconductive properties were obtained. With dichloromethane and AlCl3, a linear polymer: poly(N-methyl-3,6-carbazolyl methylene) (PMCM) was obtained. Charge transfer complexes of PMCM with acetyl-2′-hydroxyethyl-3,5-dinitrobenzoate generate a signal in the ESR spectrum, whose intensity does not depend on illumination. Films of complexes of PMCM are photoconductive with a maximum photocurrent in the visible region.

SYNTHESIS AND CHARACTERIZATION OF HIGHLY CONDUCTING, ENVIRONMENTALLY STABLE, IODINE COMPLEXES OF A SOLUBLE POLY N-METHYL 3,3' CARBAZOLYL

Poly N-methyl 3',3 carbazoly (PC) can be prepared by forming the di-Grignard reagent of 3',3 dibromo N-methyl carbazole with highly activated magnesium and subsequently adding this reagent to a tetrahydrofuran suspension containing a catalytic amount of nickle complex. The tan yellow PC isolated from this reaction mixture was soluble in a number of acceptor type solvents such as nitrobenzene. Thin, clear yellow films could be cast and were easily doped with I2, Br2 to form tough black films. Completely doped PC semiconductors containing one I atom per carbazole monomer unit, exhibited conductivities as high as 1 ohm-1cm-1 with an activation energy for D.C. conduction of 0.172 eV. Together with the featureless absorbance spectrum shown by the I2 doped films from 0.3µ to 25µ these electrical properties suggest hopping as the charge transport mechanism in these amorphous materials. The carbazole radical cations were sufficiently stable in the complexes to maintain this electrical conductivity unchanged in room air at 25°C for at least 1 month.

Delayed fluorescence of n-methylcarbazole in heptane and in toluene; energy transfer from upper excited singlet states of n-methylcarbazole to toluene

Triplet—triplet annihilation of N-methylcarbazole (NMC) leads to a primary population of upper excited singlet states Sj(NMC), j> 1, which can be detected by measurement of the delayed fluorescence (DF) Sj(NMC) → S0(NMC). With NMC in toleuen (Tol), a DF St(Tol) → S0(Tol) is observed which is caused by energy transfer from Sj(NMC) to toluene.