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A carbazole-based fluorescent probe YCN with AIE performance and a large Stokes shift (242 nm) shift was synthesized by attaching 4-acetonitrile pyridine to the 3-phenylaldehyde butylcarbazole. Its structure was characterized by 1 H NMR, 13 C NMR and MS. Probe YCN has high selectivity and sensitivity toward ONOO - . The addition of ONOO - to the probe YCN solution results in a noticeable color change from pale yellow to colorless under natural light, and a fluorescent color change from bright orange-yellow to bright yellow-green under a 365 nm UV lamp, which can be distinguished by the naked eye. The research results on the reaction mechanism showed that when YCN reacted with ONOO - , -C = C- was oxidized and broken into -CHO, and the ICT effect was significantly inhibited, resulting in changes in UV absorption and fluorescence emission phenomenon. The recognition mechanism was verified by 1 H NMR, mass spectrometry (MS) and density function theory (DFT) calculations. The experiments of live cells imaging suggested that compound YCN can be used as a fluorescent probe for the detection of ONOO - in HeLa cells. This result indicates that YCN has potential application prospects in the biological aspects., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carbazole is an aromatic heterocyclic organic compound consisting of two fused benzene rings and a pyrrole ring and is a very valuable building structure for the design of many compounds for use in various fields of chemistry and medicine. This study presents three new carbazole-based thiazole derivatives that differ in the presence of a different halogen atom: chlorine, bromine, and fluorine. Experimental studies and quantum-chemical simulations show the effect of changing a halogen atom on the physicochemical, biological, and linear and nonlinear optical properties. We have also found that carbazoles C-Cl, C-Br, and C-F exhibit high tyrosinase inhibitory activity, with IC 50 values in the range of 68-105 µM with mixed mechanism of action. Finally, molecular docking to the active site of Concanavalin A (ConA) and bioavailability for all compounds were evaluated.

In this study, we used ultraviolet-visible (UV-Vis), fluorescence, and circular dichroism (CD) techniques, as well as molecular modeling, to probe the interactions between carbazole derivatives and the G-quadruplex structure formed in the promoter region of gene Bcl-2 . This gene is a rational target for anticancer therapy due to its high expression in a variety of tumors as well as resistance to chemotherapy-induced apoptosis. We employed a sequence with a specific dual G-to-T mutation that may form a mixed-type hybrid G-quadruplex structure in the Bcl-2 P1 promoter region. The three tested carbazole compounds differing in substitution on the nitrogen atom of carbazole interact with the Bcl-2 G-quadruplex by the same binding mode with the very comparable binding affinities in the order of 10 5 M -1 . During absorption and fluorescence measurements, large changes in the ligand spectra were observed at higher G4 concentrations. The spectrophotometric titration results showed a two-step complex formation between the ligands and the G-quadruplex in the form of initial hypochromicity followed by hyperchromicity with a bathochromic shift. The strong fluorescence enhancement of ligands was observed after binding to the DNA. All of the used analytical techniques, as well as molecular modeling, suggested the π-π interaction between carbazole ligands and a guanine tetrad of the Bcl-2 G-quadruplex. Molecular modeling has shown differences in the interaction between each of the ligands and the tested G-quadruplex, which potentially had an impact on the binding strength.

A novel fluorescent sensor for the detection of Cu 2+ was developed based on carbazole derivatives. After the addition of Cu 2+ , the sensor exhibited obvious fluorescence quenching phenomenon, and the optical signal variation also enabled the sensor to quantitatively analyze Cu 2+ due to the formation of a stable 1:1 metal-ligand complex in a short time. In addition, the sensor possessed chemical reversibility and pH stability. The cell imaging and zebra fish experiments also verified its application value in biological system., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A carbazole thiophene-aldehyde and 4-methylbenzenesulfonhydrazide conjugate CSH was synthesized by introducing 5-thiophene aldehyde at the 3-position of the carbazole group as the precursor and then condensing it with 4-methylbenzenesulfonhydrazide. CSH has high selectivity and sensitivity towards ClO - , which can specifically identify ClO - by UV-Vis and fluorescence spectroscopy. CSH can rapidly respond to ClO - in the physiological pH range through a fluorescence quenching pattern, accompanied by the color of CSH changing markedly from turquoise to yellowish green under the 365 nm UV light. Probe CSH exhibits a quantitative response to ClO - (0-11 μM) with a low detection limit (1.16 × 10 -6  M). Cell imaging experiments have shown that CSH can capture fluorescent signals in the cyan and yellow channels of HeLa cells through fluorescence confocal microscopy, and can successfully identify exogenous ClO - in HeLa cells. In addition, probe CSH can also be used to detect ClO - in environmental water samples. These results indicate that CSH has potential application prospects in the environmental analysis and biological aspects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carbazole derivatives can be used as antioxidants in the lubricating oil industry. The alkylation of carbazole with 2-chloro-2-methylpropane and 2-bromopropane catalyzed by anhydrous aluminum chloride was studied. Initially, 3,6-di-iso-propylcarbazole and 3,6-di-tert-butylcarbazole were using dichloromethane and dibromomethane as solvents at room temperature, respectively. The synthesis conditions were optimized. Subsequently, the effects of reaction time, catalyst dosage, and molar ratio of carbazole to alkylating agent were investigated, and orthogonal experiments were performed. The structures of the carbazole derivatives were characterized by Fourier infrared spectroscopy (FT-IR), mass spectrum (MS) and nuclear magnetic resonance spectroscopy (NMR). The thermal stability of the synthesized carbazole derivatives was investigated by differential scanning calorimetry (DSC). The carbazole derivatives were added into the lubricating oil with a mass fraction of 0.8% and the miscibility, stability and oxidation resistance of the mixed system were evaluated by mechanical stirring and a rotary pressure vessel oxidation test (RPVOT). The DSC results showed that there was good thermal stability for the carbazole derivatives. The mechanical stirring method revealed good solubility and stability for the mixture of oil and carbazole derivatives. The RPVOT results showed that isopropyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.39 times, and tert-butyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.91 times. The antioxidant effect of tert-butyl carbazole derivatives was better than that of isopropyl carbazole derivatives., (© 2024. The Author(s).)

The persistence and potential toxicity of emergent pollutants pose significant threats to biodiversity and human health, emphasizing the need for sensors capable of detecting these pollutants at extremely low concentrations before treatment. This study focuses on the development of glassy carbon electrodes (GCEs) modified by films of poly-tris(4-(4-(carbazol-9-yl)phenyl)silanol (PTPTCzSiOH), poly-4,4'-Di(carbazol-9-yl)-1,1'-biphenyl (PCBP), and poly-1,3,5-tri(carbazol-9-yl)benzene (PTCB) for the detection of metronidazole (MNZ) in aqueous media. The films were characterized using electrochemical, microscopy, and spectroscopy techniques, including scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Monomers were electropolymerized through cyclic voltammetry and chronoamperometry techniques. Computational methods at the B3LYP/def2-TZVP level were employed to investigate the structural and electrochemical properties of the monomers. The electrochemical detection of MNZ utilized the linear sweep voltammetry technique. Surface characterization through SEM and XPS confirmed the proper electrodeposition of polymer films. Notably, MPN-GCEs exhibited higher detection signals compared to bare GCEs up to 3.6 times in the case of PTPTCzSiOH-GCEs. This theoretical study provides insights into the structural, chemical, and electronic properties of the polymers. The findings suggest that polymer-modified GCEs hold promise as candidates for the development of electrochemical sensors.

Dopamine D 3 receptor (D 3 R) is implicated in multiple psychotic symptoms. Increasing the D 3 R selectivity over dopamine D 2 receptor (D 2 R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D 3 R selective ligands. Through a structure-based virtual screen, ZLG-25 (D 3 R K i  = 685 nmol/L; D 2 R K i  > 10,000 nmol/L) was identified as a novel D 3 R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D 3 R-selective analogs with tetrahydro- β -carboline or tetrahydro- γ -carboline core. Further functional studies showed that most derivatives acted as hD 3 R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, antifungal, and antiviral agents. The aim of this study was to examine the antimicrobial potential and toxicity of newly synthesized isomeric fluorinated 4-[4-(benzylamino)butoxy]-9 H -carbazole derivatives. Their antimicrobial activity against bacteria and fungi was tested according to CLSI guidelines. Similarly to previously studied carbazole-containing compounds, the tested derivatives showed the ability to effectively inhibit the growth of Gram-positive bacteria. The addition of carbazole derivatives 2 , 4 , and 8 at the concentration of 16 µg/mL caused the inhibition of S. aureus growth by over 60%. The MIC value of compounds 2 - 5 and 7 - 10 was 32 µg/mL for Staphylococcus strains. Gram-negative strains of E. coli and P. aeruginosa were found to be more resistant to the tested carbazole derivatives. E. coli cells treated with compounds 3 and 8 at a concentration of 64 µg/mL resulted in a greater-than-40% reduction in bacterial growth. In the case of the P. aeruginosa strain, all compounds in the highest concentration that we tested limited growth by 35-42%. Moreover, an over-60% inhibition of fungal growth was observed in the cultures of C. albicans and A. flavus incubated with 64 µg/mL of compounds 2 or 7 and 1 or 4 , respectively. The hemolysis of red blood cells after their incubation with the tested carbazole derivatives was in the range of 2-13%. In the case of human fibroblast cells, the toxicity of the tested compounds was higher. Derivative 1 , functionalized with fluorine in position 2 and its hydrobromide, was the least toxic. The obtained results indicated the antimicrobial potential of the tested 4-[4-(benzylamino)butoxy]-9 H -carbazole derivatives, especially against S. aureus strains; therefore, it is worth further modifying these structures, in order to enhance their activity against pathogenic microorganisms.

Carbazole alkaloids, as an important class of natural products, have been widely reported to have extensive biological activities. Based on our previous three-component reaction to construct carbazole scaffolds, we introduced a methylene group to provide a rotatable bond, and designed series of carbazole derivatives with structural diversity including carbazole amide, carbazole hydrazide and carbazole hydrazone. All synthesized carbazole derivatives were evaluated for their in vitro cytotoxic activity against 7901 (gastric adenocarcinoma), A875 (human melanoma) and MARC145 (African green monkey kidney) cell lines. The preliminary results indicated that compound 14a exhibited high inhibitory activities on 7901 and A875 cancer cells with the lowest IC 50 of 11.8 ± 1.26 and 9.77 ± 8.32 μM, respectively, which might be the new lead compound for discovery of novel carbazole-type anticancer agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Chen, Nie, Chen, Cao and Ke.)

Microbial infection is a leading cause of death worldwide, resulting in around 1.2 million deaths annually. Due to this, medicinal chemists are continuously searching for new or improved alternatives to combat microbial infections. Among many nitrogen-containing heterocycles, carbazole derivatives have shown significant biological activities, of which its antimicrobial and antifungal activities are the most studied. In this review, miscellaneous carbazole derivatives and their antimicrobial activity are discussed (articles published from 1999 to 2022).

1H-Indole-3-carbaldehyde and related members of the indole family are ideal precursors for the synthesis of active molecules. 1H-Indole-3-carbaldehyde and its derivatives are essential and efficient chemical precursors for generating biologically active structures. Multicomponent reactions (MCRs) offer access to complex molecules. This review highlights the recent applications of 1H-indole-3-carbaldehyde in such inherently sustainable multicomponent reactions from the period, 2014 to 2021 and provides an overview of the field that awaits further exploitation in the assembly of pharmaceutically interesting scaffolds., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Since more than 85% of lung cancer cases are non-small cell lung cancer (NSCLC), finding novel agents with anti-tumor activities is meaningful for NSCLC patients. Mitochondria is essential for cellular energy metabolism in cancer, and regulating mitochondrial bioenergetics is emerging as a practical approach for cancer treatment and prevention. The carbazole scaffold is an active structure showing anti-cancer biological activity, and the structural diversity has been expanded through the improvement and optimization of synthesizing methods. To find novel carbazole derivatives with great anti-tumor potential and explore structures variety, we designed and synthesized a series of 9-(pyrimidin-2-yl)-9H-carbazole derivatives based on the previously reported Cp∗Rh(III)/H + tandem catalytic system. With thoroughly bioactivity exploration, we found benzo[d] [1,3]dioxol-5-yl(9-(pyrimidin-2-yl)-9H-carbazol-1-yl)methanone (compound 5n) showed notable activity in disrupting the mitochondrial homeostasis, induced cell cycle arrest and apoptosis in human adenocarcinoma cells, and finally showed anti-tumor activity in an NSCLC-xenograft mice model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The environmental presence of anions of natural origin or anthropogenic origin is gradually increasing. As a tool to tackle this problem, carbazole derivatives are an attractive gateway to the development of luminescent chemosensors. Considering the different mechanisms proposed for anion recognition, the fluorescence properties and anion-binding response of several newly synthesised carbazole derivatives were studied. Potential anion sensors were designed so that they combined the native fluorescence of carbazole with the presence of hydrogen bonding donor groups in critical positions for anion recognition. These compounds were synthesised by a feasible and non-expensive procedure using palladium-promoted cyclodehydrogenation of suitable diarylamine under microwave irradiation. In comparison to the other carbazole derivatives studied, 1-hydroxycarbazole proved to be useful as a fluorescent sensor for anions, as it was able to sensitively recognise fluoride and chloride anions by establishing hydrogen bond interactions through the hydrogen atoms on the pyrrolic nitrogen and the hydroxy group. Solvent effects and excited-state proton transfer (ESPT) of the carbazole derivatives are described to discard the role of the anions as Brönsted bases on the observed fluorescence behaviour of the sensors. The anion-sensor interaction was confirmed by 1 H-NMR. Molecular modelling was employed to propose a mode of recognition of the sensor in terms of complex stability and interatomic distances. 1-hydroxycarbazole was employed for the quantitation of fluoride and chloride anions in commercially available medicinal spring water and mouthwash samples.

In recent years, studies on the organic small molecule fluorescent probes targeting G-quadruplexes have attracted a wide attention, because G-quadruplexes play an important role in various biological functions. Herein, we reported three crescent-shaped carbazole derivatives (4a-4c) and studied their interactions with the single-stranded, duplex, G-quadruplex and i-motif DNA. Both 4b and 4c have an above 100 nm Stokes shift and low fluorescence intensity, moreover, they exhibit the stronger affinity to G-quadruplex than to the other DNA structures. 4b with a cyanovinyl pyridine salt group displays a specific light-up fluorescence response to G-quadruplexes. FRET and CD results suggest that both 4b and 4c are able to improve the stability of G-quadruplexes and maintain their topology, moreover, they induce G-rich sequences (bcl-2, HTG, and KSS) to fold into G-quadruplexes in Na + /K + free buffer. In addition, CLSM images suggest that 4b and 4c are mainly distributed in the mitochondrion of living HepG2 cells, and a weak fluorescence signal is also observed in the nucleus for 4c. Given that the two compounds have the larger association constants to G-quadruplexes over to duplex and single-stranded DNA, we speculate that the fluorescence signals in cells may mainly be attributed to the compound/G-quadruplex DNA complexes., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, causes neonatal pig acute gastrointestinal infection with a characterization of severe diarrhea, vomiting, high morbidity, and high mortality, resulting in tremendous damages to the swine industry. Neither specific antiviral drugs nor effective vaccines are available, posing a high priority to screen antiviral drugs. The aim of this study is to investigate anti-PEDV effects of carbazole alkaloid derivatives. Eighteen carbazole derivatives (No.1 to No.18) were synthesized, and No.5, No.7, and No.18 were identified to markedly reduce the replication of enhanced green fluorescent protein (EGFP) inserted-PEDV, and the mRNA level of PEDV N. Flow cytometry assay, coupled with CCK8 assay, confirmed No.7 and No.18 carbazole derivatives displayed high inhibition effects with low cell toxicity. Furthermore, time course analysis indicated No.7 and No.18 carbazole derivatives exerted inhibition at the early stage of the viral life cycle. Collectively, the analysis underlines the benefit of carbazole derivatives as potential inhibitors of PEDV, and provides candidates for the development of novel therapeutic agents.

Fullerene host-guest constructs have attracted increasing attention owing to their molecular-level hybrid arrangements. However, the usage of simple carbazolic derivatives to bind with fullerenes is rare. In this research, three novel carbazolic derivatives, containing a tunable bridging linker and carbazole units for the capturing of fullerenes, are rationally designed. Unlike the general concave-convex interactions, fullerenes could interact with the planar carbazole subunits to form 2-dimensional hexagonal/quadrilateral cocrystals with alternating stacking patterns of 1 : 1 or 1 : 2 stoichiometry, as well as the controllable fullerene packing modes. At the meanwhile, good electron-transporting performances and significant photovoltaic effects were realized when a continuous C 60⋅⋅⋅ C 60 interaction channel existed. The results indicate that the introduction of such carbazolic system into fullerene receptor would provide new insights into novel fullerene host-guest architectures for versatile applications., (© 2021 Wiley-VCH GmbH.)

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily primed PCR to analyze their intrinsic DNA damage-inducing and DNA methylation-changing abilities. We demonstrate that small modifications in the substitution patterns of carbazoles can have profound effects on their intrinsic genotoxic and epigenetic properties, with PK9320 and PK9323 being eligible candidates as "anticancer compounds" and "anticancer epi-compounds" and PK083 a "damage-corrective" compound on human breast adenocarcinoma cells. Such different properties may be exploited for their use as anticancer agents and chemical probes.

Recently, a series of carbazole derivatives containing chalcone analogues (CDCAs) were synthetized as potent anticancer agents and apoptosis inducers. These compounds target the inhibition of topoisomerase II and present cytotoxic activities. After comparison to experiment, we validated the use of B3LYP, a density functional theory-based approach, to describe the structure and molecular properties of the carbazole subunit and CDCAs compounds of interest. Then, we derived relationships between the chemical descriptors and activity of these carbazole derivatives using multi-parameter optimization and quantitative structure activity relationships (QSAR) approaches. For the QSAR studies, we used multiple linear regression and artificial neural network statistical modelling. Our predicted activities are in good agreement with the experimental ones. We found that the most important parameter influencing the activity of the considered compounds is the octanol-water partition coefficient, highlighting the importance of flexibility as a key molecular parameter to favor cell membrane crossing and enhance the action of these CDCAs against topoisomerase II. Our results provide useful guidelines for designing new oral active CDCAs medicaments for cytotoxic inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Polycarbazole and its derivatives have been extensively used for the last three decades, although the interest in these materials briefly decreased. However, the increasing demand for conductive polymers for several applications such as light emitting diodes (OLEDs), capacitators or memory devices, among others, has renewed the interest in carbazole-based materials. In this review, the synthetic routes used for the development of carbazole-based polymers have been summarized, reviewing the main synthetic methodologies, namely chemical and electrochemical polymerization. In addition, the applications reported in the last decade for carbazole derivatives are analysed. The emergence of flexible and wearable electronic devices as a part of the internet of the things could be an important driving force to renew the interest on carbazole-based materials, being conductive polymers capable to respond adequately to requirement of these devices.

In this work, a series of fluorescent cathodically coloring electrochromic (EC) small molecules o - , m - , and p -DBFDCz with 3,5-di(9 H -carbazol-9-yl)benzene (DCz) linked to dibenzofuran (DBF) at different substitutional positions were synthesized and fully characterized. These compounds are electroactive and undergo quasi-reversible two-step single-electron reduction generating radical anions and dianions. The absorptions of o - , m - , and p -DBFDCz in the neutral states lie in the UV region (λ onset ≈ 350 nm), showing high transparency, while the absorption of their reduced states can be largely tuned across the visible region through driving voltage and substitutional positions. Initially generated spectroelectrochemically radical anions show absorption in the short-wavelength region of ∼380-500 nm with weak broad absorptions at longer wavelengths. On further reduction, these bands disappear on the cost of growing intense bands from dianions at longer wavelengths of 500-700 nm with some tail absorptions in the shorter-wavelength region. This renders the colors of the EC devices based on these materials, which are changed from green to red, yellow to magenta, and light to deep blue for o - , m - , and p -DBFDCz , respectively, covering four legs of the L * a * b * color space. Besides excellent optical contrast (>90%) and high coloration efficiency (up to 504 cm 2 C -1 ), the fluorescence observed in solution of neutral o - , m - , and p -DBFDCz can be modulated between the fluorescence and quenched states by direct electrochemical redox reactions. Both EC and electrofluorochromic (EFC) processes are reversible on cycling. This research demonstrates the feasibility of developing multifunctional EC/EFC materials with multicolored electrochromism through exploiting electrochemical properties of traditional fluorescent small molecules.

Colorimetric sensors from N-butyl-3,6-disubstituted carbazole derivatives containing nitroazobenzene (1) and nitrobenzene (2) were designed, synthesized and compared for their anion sensing ability. Computational simulations were undertaken to determine the optimum geometry of 1. Anion sensing studies revealed that selectivity in anion detection depended on the polarity of solvent, acidity of binding unit and basicity of the anion. The ability to sense via naked eye observations using the strong basic anions (F - and CN - ) for both sensors arises from a deprotonation process at the binding sites attributed to the intramolecular charge transfer transition at the sensory unit. The discrimination of F - from CN - has been achieved by the optimization of solvent polarity. Sensor 1 offers a promising property over sensor 2 with a lower detection limit, a few of anion interference and higher stability., (Copyright © 2019. Published by Elsevier B.V.)

Microwave formylation of carbazole derivatives was investigated and 3-monoaldehydes were obtained in high yield. A potential DNA-binding ligand, 3-[(3-ethyl)-2-vinylbenzothiazolium]-9- N -ethyl carbazole iodide, was synthesized and characterized including spectral properties (UV-Vis absorption and fluorescence spectra). The binding selectivity and affinity of three carbazole ligands for double-stranded and G-quadruplex DNA structures were studied using a competitive dialysis method in sodium- and potassium-containing buffer solutions.

We have introduced a novel water-soluble two-photon photoinitiator based on the host-guest interaction between 3,6-bis[2-(1-methyl-pyridinium)vinyl]-9-pentyl-carbazole diiodide (BMVPC) and cucurbit[7]uril (CB7) because most of the commercial photoinitiators have poor two-photon initiating efficiency in aqueous solutions. The binding ratio of BMVPC and CB7 was determined as 1:1 by isothermal titration calorimetry and quantum chemical calculation. The formation of the host-guest complex increases the two-photon absorption cross-section about five times, and improves the water solubility required as the photoinitiator for hydrogel fabrication. The BMVPC-CB7 inclusion complex was used as the one-component photoinitiator, and the polyethylene glycol diacrylate with promising biocompatibility was used as the hydrogel monomer to form the aqueous-phase photoresist system applied to two-photon polymerization microfabrication. A relatively low laser threshold of 4.5 mW, a high fabricating resolution of 180 nm, and the true three-dimensional (3D) fabricating capability in the aqueous solution have been obtained by using the as-prepared photoresist system. Finally, 3D engineering hydrogel scaffold microstructures with low toxicity and good biocompatibility have been fabricated and cocultured with living HeLa cells, which demonstrates the potential for further application in tissue engineering.

Background: Autotaxin-LPA signaling has been implicated in cancer progression, and targeted for the discovery of cancer therapeutic agents., Objective: Potential ATX inhibitors were synthesized to develop novel leading compounds and effective anticancer agents., Methods: The present work designs and synthesizes a series of 2,7-subsitituted carbazole derivatives with different terminal groups R [R = -Cl (I), -COOH (II), -B(OH)2 (III), or -PO(OH)2 (I-IV)]. The inhibition of these compounds on the enzymatic activity of ATX was measured using FS-3 and Bis-pNpp as substrates, and the cytotoxicity of these compounds was evaluated using SW620, SW480, PANC-1, and SKOV-3 human carcinoma cells. Furthermore, the binding of leading compound with ATX was analyzed by molecular docking., Results: Compound III was shown to be a promising antitumor candidate by demonstrating both good inhibition of ATX enzymatic activity and high cytotoxicity against human cancer cell lines. Molecular docking study shows that compound III is located in a pocket, which mainly comprises amino acids 209 to 316 in domain 2 of ATX, and binds with these residues of ATX through van der Waals, conventional hydrogen bonds, and hydrophobic interactions., Conclusion: Compound III with the terminal group R = -B(OH)2 has the most potent inhibitory effect with the greatest cytotoxicity to cancer cells. Moreover, the docking model provides a structural basis for the future optimization of promising antitumor compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Synthetic or natural carbazole derivatives constitute an interesting class of heterocycles, which showed several pharmaceutical properties and occupied a promising place as antitumour tools in preclinical studies. They target several cellular key-points, e.g. DNA and Topoisomerases I and II. The most studied representative, i.e. Ellipticine, was introduced in the treatment of metastatic breast cancer. However, because of the onset of dramatic side effects, its use was almost dismissed. Many efforts were made in order to design and synthesise new carbazole derivatives with good activity and reduced side effects. The major goal of the present study was to synthesise a series of new N-thioalkylcarbazole derivatives with anti-proliferative effects. Two compounds, 5a and 5c, possess an interesting anti-proliferative activity against breast and uterine cancer cell lines without affecting non-tumoural cell lines viability. The most active compound (5c) induces cancer cells death triggering the intrinsic apoptotic pathway by inhibition of Topoisomerase II.

The interactions of c-myc G-quadruplex with three carbazole derivatives were investigated by UV-Vis spectrophotometry, fluorescence, CD spectroscopy, and molecular modeling. The results showed that a combination of carbazole scaffold functionalized with ethyl, triazole and imidazole groups resulted in stabilization of the intramolecular G-quadruplex formed by the DNA sequence derived from the NHE III 1 region of c-myc oncogene (Pu22). Binding to the G-quadruplex Pu22 resulted in the significant increase in fluorescence intensity of complexed ligands 1-3. All ligands were capable of interacting with G4 DNA with binding stoichiometry indicating that two ligand molecules bind to G-quadruplex with comparable affinity, which agrees with binding model of end-stacking on terminal G-tetrads., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The binding affinities of three carbazole derivatives to the intramolecular G-quadruplex (GQ) DNA formed by the sequence 5′-AGGGAGGGCGCTGGGAGGAGGG-3′, derived from the c-KIT 1 oncogene region, were investigated. All carbazole cationic ligands that differed in the substituents on the nitrogen atom were able to stabilize G-quadruplex, as demonstrated using UV-Vis, fluorescence and CD spectroscopic techniques as well as molecular modeling. The spectrophotometric titration results showed spectral features characteristic of these ligands-bathochromic shifts and initial hypochromicity followed by hyperchromicity at higher GQ concentrations. All free carbazole ligands exhibited modest fluorescent properties, but after binding to the DNA the fluorescence intensity increased significantly. The binding affinities of carbazole ligands to the c-KIT 1 DNA were comparable showing values in the order of 10⁵ M −1 . Molecular modeling highlights the differences in interactions between each particular ligand and studied G-quadruplex, which potentially influenced binding strength. Obtained results relevant that all three investigated ligands have stabilization properties on studied G-quadruplex., Competing Interests: The authors declare no conflict of interest.

Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus) prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection., Methods: Six chloro-1,4-dimethyl-9 H -carbazoles ( 2a , b - 4a , b ) have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli β-galactosidase expressing CD4⁺, CXCR4⁺, CCR5⁺ TZM-bl cells., Results and Conclusion: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9 H -carbazoles has been carried out. Among all tested compounds, a nitro-derivative ( 3b ) showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs., Competing Interests: The authors declare no conflict of interest.

DNA-binding agents have been considered as an established opportunity for the development of anticancer drugs and DNA fluorescence probes. This work reported the synthesis of two novel carbazole derivatives (1 and 2) and investigated their DNA binding properties, living cell image, and cytotoxicity. The results demonstrated that both compounds presented the higher binding affinity to G-quadruplex than to duplex DNA by means of UV-Vis absorption titration and fluorescent intercalator displacement. Continuous variation analysis indicated that their binding stoichiometries of the compound/G-quadruplex were near 2 except the compound/bcl-2. Circular dichroism spectra showed that both compounds had no influence on the conformation of G-quadruplexes. Fluorescence titrations indicated that 2 had the potential to be a G-quadruplex selective fluorescent probe, while 1 could be used as a fluorescent probe for duplex DNA. Confocal fluorescence images indicated that both compounds could enter the living HepG2 cells, and 1 mainly located in nucleus whereas 2 mainly distributed in cytoplasm. DNase and RNase digest tests indicated that both compounds could enter into the nucleus and interact with duplex DNA, especially, 2 could interact with RNA and/or G-quadruplex DNA. They also exhibited an obvious antiproliferative activity to HepG2 by using MTT assays, with IC 50 values of 2.7 and 9.5 μM for 1 and 2, respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The three title compounds, C 26 H 19 NO 3 S, (1), C 27 H 20 N 2 O 8 S, (2), and C 30 H 19 NO 3 S, (3), are carbazole derivatives, where (1) and (3) are heterocycle-containing carbazoles with a benzo-furan moiety fused to a carbazole unit. In (2), a di-meth-oxy-nitro-phenyl ring is attached to the carbazole moiety. In the three derivatives, a phenyl-sulfonyl group is attached to the N atom of the carbazole unit. Compound (1) crystallizes with two independent mol-ecules in the asymmetric unit ( A and B ). The carbazole skeleton in the three compounds is essentially planar. In compound (1), the benzene ring of the phenyl-sulfonyl moiety is almost orthogonal to the carbazole moiety, with dihedral angles of 85.42 (9) and 84.52 (9)° in mol-ecules A and B , respectively. The benzene ring of the phenyl-sulfonyl group in compounds (2) and (3) are inclined to the carbazole moiety, making dihedral angles of 70.73 (13) and 81.73 (12)°, respectively. The S atom has a distorted tetra-hedral configuration in all three compounds. In the crystals, C-H⋯O hydrogen bonds give rise to R 2 2 (12) inversion dimers for compound (1), and to R 2 2 (24) inversion dimers and R 4 4 (40) ring motifs for compound (2). The crystal packing in (1) also features C-H⋯π and π-π inter-actions [shortest inter-centroid distance = 3.684 (1) Å], leading to supra-molecular three-dimensional aggregation. In the crystal of compound (2), the combination of the various C-H⋯O hydrogen bonds leads to the formation of a three-dimensional network. In the crystal of compound (3), mol-ecules are linked by C-H⋯O hydrogen bonds, forming chains running parallel to the a axis, and the chains are linked by C-H⋯π inter-actions, forming corrugated sheets parallel to the ab plane.

The title compounds, C 30 H 18 N 2 O 5 S, (I), and C 27 H 18 N 2 O 4 S 2 , (II), are carbazole derivatives with a phenyl-sulfonyl group and a nitro-phenyl group attached to the carbazole moiety in identical positions in both mol-ecules. A benzo-furan ring system in (I) and a methyl-thio-phene ring in (II) are fused with the respective carbazole moieties on the same sides. The mean plane of the carbazole ring system makes a dihedral angle of 3.17 (7)° with the benzo-furan ring system in (I) and a dihedral angle of 3.39 (11)° with the methyl-thio-phene ring in (II), implying that both fused units are essentially planar. The mean planes of the carbazole ring systems in both the compounds are almost orthogonal to the respective nitro-substituted phenyl rings, making dihedral angles of 75.64 (10) and 77.63 (12)° in compounds (I) and (II), respectively. In (I), the phenyl-sulfonyl ring system is positionally disordered with a refined occupancy ratio of 0.63 (2):0.37 (2). In both compounds, the mol-ecular structures are stabilized by intra-molecular C-H⋯O hydrogen bonds, generating S (6) ring motifs with the sulfone group O atoms. In the crystal of compound (I), mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, which generate R 2 2 (18) inversion dimers, and inter-connected by C (14) chains running along the c -axis direction, whereas in compound (II), the C-H⋯O hydrogen bonds generate R 4 3 (37) ring motifs. In the crystals of both compounds, C-H⋯O hydrogen-bonded sheets are formed lying parallel to (10-1). In addition, C-H⋯π and offset π-π inter-actions [inter-centroid distance = 3.7158 (14) Å in (I) and 3.9040 (15) Å in (II)] are also present in the crystals of both compounds.

Series of N -substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N -substituted carbazoles as potential anti-MRSA agents.

In this study, we report fluorescent organic nanoprobes with intense blue, green, and orange-red emissions prepared by self-assembling three carbazole derivatives into nanorods/nanoparticles. The three compounds consist of two or four electron-donating carbazole groups linked to a central dicyanobenzene electron acceptor. Steric hindrance from the carbazole groups leads to noncoplanar 3D molecular structures favorable to fluorescence in the solid state, while the donor-acceptor structures endow the molecules with good two-photon excited emission properties. The fluorescent organic nanoprobes exhibit good water dispersibility, low cytotoxicity, superior resistance against photodegradation and photobleaching. Both one- and two-photon fluorescent imaging were shown in the A549 cell line. Two-photon fluorescence imaging with the fluorescent probes was demonstrated to be more effective in visualizing and distinguishing cellular details compared to conventional one-photon fluorescence imaging.

Carbazole skeleton is the key structural motif of many biologically active compounds including synthetic and natural products. Over the past several years, a large number of research highlighting the significance of carbazole derivatives has been reported in the literature. The present review focuses on the recent progress, from 2010 until now, in knowledge on various biological properties of classical, tricyclic carbazole derivatives., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

We designed carbazole unit with an extended π conjugation by employing Vilsmeier formylation reaction and Knoevenagel condensation to facilitate the functional groups of quinoline from 3- or 3,6-position of carbazole. Two compounds doped with poly(methyl methacrylate) (PMMA) films were prepared. To explore the electronic transition properties of these compounds, one-photon absorption properties were experimentally measured and theoretically calculated by using the time-dependent density functional theory. We surveyed these films by using an 800 nm Ti:sapphire 120-fs laser with two-photon absorption (TPA) fluorescence emission properties and TPA coefficients to obtain the TPA cross sections. A three-dimensional optical data storage experiment was conducted by using a TPA photoreaction with an 800 nm-fs laser on the film to obtain a seven-layer optical data storage. The experiment proves that these carbazole derivatives are well suited for two-photon 3D optical storage, thus laying the foundation for the research of multilayer high-density and ultra-high-density optical information storage materials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Here we present the synthesis, pharmacological activity, and molecular docking of novel non-competitive antagonists of GluK2 receptor. The compounds concerned are derivatives of indole and carbazole and are the second reported series of non-competitive antagonists of the GluK2 receptor (the first one was also published by our group). The activity of the indole derivatives is in the micromolar range, as in the case of the first series of non-competitive GluK2 receptor antagonists. We have found that designed carbazole derivatives are devoid of activity. Active indole derivatives interact with the transduction domain of the GluK2 receptor, i.e., the domain which links the transmembrane region of the receptor with the agonist-binding domain. The binding pocket is situated within one receptor subunit.

In the title carbazole derivative, C32H32N2, the mol-ecule resides on a crystallographic twofold axis, which runs through the central C-C bond. The carbazole ring system is almost planar, with a maximum deviation of 0.041 (1) Å for one of the ring-junction C atoms. The crystal packing is stabilized by C-H⋯π inter-actions only, which form a C(7) chain-like arrangement along [110] in the unit cell.

In order to increase the polarity of the potent CB2 ligand 1a, the homologous hydroxyalkyl carbazoles 2a-c were prepared and pharmacologically evaluated. An important step in the synthesis is the hydroxyalkylation of carbazole with cyclic sulfates providing the 2-hydroxyethyl and 3-hydroxypropyl derivatives 5a and 5b in a one-step reaction. The final propionamides 2a-c were prepared using the recently reported coupling reagent COMU®. The X-ray crystal structure of 2c displays an almost coplanar arrangement of the 3-phenyl-1,2,4-oxadiazole biaryl system. The increased polarity of 2a is associated with an almost 100-fold reduced CB2 affinity. The 3-hydroxypropyl derivative 2b represents the best compromise between lipophilicity and CB2 affinity (Ki  = 33 nM)., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A convergent strategy was followed to modify systematically carbazole based CB(2) receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB(2) affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (Ki=5.8nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB(2) receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB(2) affinity together with the high selectivity over the CB(2) subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)