ABSTRACT
CONTEXT: For the first time, the use of monocyclic rings C18 and B9N9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C18 and B9N9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C18 and B9N9 rings of the complexes. METHODS: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B9N9, MKN@B9N9, MRY@B9N9, and THC@B9N9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C18, MKN@C18, MRY@C18, and THC@C18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B9N9 and C18, the analyte recovery time for C18 is much shorter (9.91 × 10-11 for THC@C18) than that for B9N9 shorter recovery time value of 3.75 × 10-9 for EPT@B9N9. These results suggest that our reported sensors B9N9 and C18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B9N9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications.
Subject(s)
Antineoplastic Agents , Carbazoles , Density Functional Theory , Carbazoles/chemistry , Antineoplastic Agents/chemistry , Adsorption , Electrochemical Techniques/methods , Models, Molecular , Molecular StructureABSTRACT
Herein, two poly(3-aminocarbazole) derivatives containing imidazole N-type acceptor were synthesized and reported, which are named PCPI and PCBI respectively. The fluorescence spectrum shows that PCPI (Em = 498 nm) and PCBI (Em = 398 nm) both have a strong fluorescence emission. It is worth noting that PCPI has a larger stokes shift of 153 nm, which is beneficial for improving the sensitivity of the sensor and enhancing its anti-interference ability. As expected, our experimental results indicate that both PCPI and PCBI can cause a specific response of "fluorescence OFF" to Hg2+ compared with other ions. And PCPI and PCBI both have excellent detection capabilities for Hg2+, with detection limits of 69.8 nM and 11.4 nM respectively. Moreover, PCBI exhibits excellent absorption of Hg2+ with a maximum absorption capacity of 477.8 mg/g at 20 °C. It indicates that PCBI can be used as a functional material for the detection and removal of Hg2+ in water.
Subject(s)
Carbazoles , Mercury , Water Pollutants, Chemical , Mercury/analysis , Mercury/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Adsorption , Carbazoles/chemistry , Water/chemistry , Spectrometry, Fluorescence , Polymers/chemistry , Limit of DetectionABSTRACT
Ten undocumented carbazole derivatives (2-11) along with the reported analogue (1) were isolated from the mangrove-derived Streptomyces sp. OUCMDZ-5511, cultured with NaBr-supplemented liquid medium. Compounds 1-7 are brominated carbazoles, and 8, 10, and 11 feature an additional thiazole or 2,3-dihydro-1,4-oxathiine rings, respectively. Their structures were identified through spectroscopic techniques, computational chemistry, and X-ray crystallography. Notably, compounds 6 and 8 effectively inhibited immune cell migration, indicating anti-inflammatory activity in vivo, potentially via Myd88/Nf-κB pathways, as suggested for compound 6.
Subject(s)
Carbazoles , Streptomyces , Streptomyces/chemistry , Carbazoles/chemistry , Carbazoles/pharmacology , Carbazoles/isolation & purification , Molecular Structure , Crystallography, X-Ray , Bromine/chemistry , Sulfur/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Marine Biology , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , AnimalsABSTRACT
To find novel inhibitors of α-glucosidase and α-amylase, a series of new carbazole-oxadiazole derivatives (6a-6n) were prepared, and screened for their anti-α-glucosidase and anti-α-amylase effects. Most of the tested derivatives showed different degrees of α-glucosidase and α-amylase inhibitory activity (IC50: 21.39 ± 0.69-92.05 ± 1.54 µM, 45.53 ± 1.50-126.14 ± 6.33 µM, respectively) compared to the standard acarbose (IC50: 427.00 ± 9.56 µM, 24.68 ± 1.10 µM, respectively). Thereinto, 6c (IC50 = 21.39 ± 0.69 µM) displayed the most effective anti-α-glucosidase activity and 6e presented the best anti-α-amylase activity with an IC50 value of 45.53 ± 1.50 µM. Lineweaver-Burk plot analysis suggested that 6c and 6e behaved as mixed α-glucosidase inhibitor and mixed α-amylase inhibitor, respectively. The results of circular dichroism, atomic force microscope, and molecular docking simulation exposed interaction mechanisms between two preferred compounds (6c and 6e) and their corresponding enzymes. Combined with the possible properties of reducing the elevation in postprandial blood glucose, oral activity, positive bioavailability, and low cytotoxicity of 6c and 6e, it could be concluded that the target derivatives may be able to act as lead molecules for the development of new hypoglycemic agents.
Subject(s)
Carbazoles , Drug Design , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Oxadiazoles , alpha-Amylases , alpha-Glucosidases , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , alpha-Glucosidases/metabolism , Oxadiazoles/chemistry , Oxadiazoles/pharmacology , Oxadiazoles/chemical synthesis , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Carbazoles/chemistry , Carbazoles/pharmacology , Carbazoles/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Humans , Animals , Dose-Response Relationship, Drug , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/chemical synthesis , Rats , MaleABSTRACT
Organic luminescent radicals are a new class of materials with potential applications not only in light-emitting devices but also in the biochemistry field. New tris(2,4,6-trichlorophenyl)methyl (TTM) radicals with alkoxy-substituted carbazole donors were synthesized and characterized. PEG-substituted carbazole-TTM was found to be water-soluble. The water-soluble TTM radical aqueous solution showed fluorescence at 777 nm and the ability to shorten the longitudinal relaxation time (T1) of water. The concept of water-soluble luminescent radicals is expected to be used to develop a potential fluorescence and MR dual-use imaging moiety.
Subject(s)
Carbazoles , Solubility , Water , Carbazoles/chemistry , Carbazoles/chemical synthesis , Water/chemistry , Free Radicals/chemistry , Luminescence , Molecular Structure , Luminescent Agents/chemistry , Luminescent Agents/chemical synthesisABSTRACT
DNA methyltransferase 1 (DNMT1) is the primary enzyme responsible for maintaining DNA methylation patterns during cellular division, crucial for cancer development by suppressing tumor suppressor genes. In this study, we retained the phthalimide structure of N-phthaloyl-l-tryptophan (RG108) and substituted its indole ring with nitrogen-containing aromatic rings of varying sizes. We synthesized 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids and confirmed them as DNMT1 inhibitors through protein affinity testing, radiometric method using tritium labeled SAM, and MTT assay. Preliminary structure-activity relationship analysis revealed that introducing substituents on the carbazole ring could enhance inhibitory activity, with S-configuration isomers showing greater activity than R-configuration ones. Notably, S-3-(3,6-di-tert-butyl-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7r-S) and S-3-(1,3,6-trichloro-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7t-S) exhibited significant DNMT1 enzyme inhibition activity, with IC50 values of 8.147 µM and 0.777 µM, respectively (compared to RG108 with an IC50 above 250 µM). Moreover, they demonstrated potential anti-proliferative activity on various tumor cell lines including A2780, HeLa, K562, and SiHa. Transcriptome analysis and KEGG pathway enrichment of K562 cells treated with 7r-S and 7t-S identified differentially expressed genes (DEGs) related to apoptosis and cell cycle pathways. Flow cytometry assays further indicated that 7r-S and 7t-S induce apoptosis in K562 cells and arrest them in the G0/G1 phase in a concentration-dependent manner. Molecular docking revealed that 7t-S may bind to the methyl donor S-adenosyl-l-methionine (SAM) site in DNMT1 with an orientation opposite to RG108, suggesting potential for deeper penetration into the DNMT1 pocket and laying the groundwork for further modifications.
Subject(s)
Carbazoles , Cell Proliferation , DNA (Cytosine-5-)-Methyltransferase 1 , Enzyme Inhibitors , Humans , Structure-Activity Relationship , Carbazoles/pharmacology , Carbazoles/chemistry , Carbazoles/chemical synthesis , DNA (Cytosine-5-)-Methyltransferase 1/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Cell Proliferation/drug effects , Molecular Structure , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Screening Assays, Antitumor , Dose-Response Relationship, Drug , Indoles/pharmacology , Indoles/chemistry , Indoles/chemical synthesis , Molecular Docking Simulation , Cell Line, Tumor , Phthalimides , Tryptophan/analogs & derivativesABSTRACT
7H-Dibenzo[c,g]carbazole (DBC) is a prevalent environmental contaminant that induces tumorigenesis in several experimental animals. Recently, it has been utilized to develop high-performance solar cells and organic phosphorescent materials. It is imperative to strengthen investigations of DBC metabolism to understand its potential risks to human health. In this study, human CYP1A1 was employed as the metabolic enzyme to investigate the metabolic mechanism of DBC by molecular docking, molecular dynamics (MD) simulation, and quantum mechanical (QM) calculation. The results indicate that DBC binds to CYP1A1 in two modes (mode 1 and mode 2) mainly through nonpolar solvation energies (ΔGnonpolar). The formation of the two binding modes is attributed to the anchoring effect of the hydrogen bond formed by DBC with Asp320 (mode 1) or Ser116 (mode 2). Mode 1 is a "reactive" conformation, while mode 2 is not considered a "reactive" conformation. C5 is identified as the dominant site, and the pyrrole nitrogen cannot participate in the metabolism. DBC is metabolized mainly by a distinct electrophilic addition-rearrangement mechanism, with an energy barrier of 21.74 kcal/mol. The results provide meaningful insights into the biometabolic process of DBC and contribute to understanding its environmental effects and health risks.
Subject(s)
Carbazoles , Cytochrome P-450 CYP1A1 , Molecular Docking Simulation , Molecular Dynamics Simulation , Carbazoles/chemistry , Carbazoles/metabolism , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A1/chemistry , Humans , Quantum Theory , Hydrogen BondingABSTRACT
As emerging organic contaminants, Polyhalogenated carbazoles (PHCZs) have caused wide concerns due to their wide distribution in the environment and dioxin-like toxicity. Nevertheless, research on the distribution and formation mechanisms of PHCZs in polluted environment of printing and dyeing plants is lacking. Here, 11 PHCZs were detected in samples from the Cao'e River, China, a typical river heavily polluted by printing and dyeing. The PHCZs concentrations in the soil, sediment, and water samples were 8.3-134.5 ng/g (median: 26.3 ng/g), 17.7-348.8 ng/g (median: 64.2 ng/g), and 1.2-41.4 µg/L (median: 4.8 µg/L), respectively. 3,6-dichlorocarbazole was the dominant congener, proved by both analysis results and formation mechanisms. PHCZ migration patterns in water-sediment systems indicated that highly halogenated PHCZs tend to be transferred to sediment. Furthermore, PHCZs are persistent, can undergo long-range transport, and pose high risks to aquatic organisms by models. PHCZs released from dye production into environment can be form through halogenation of carbazole or PHCZs formed during the dye synthesis, heating of halogenated indigo dyes, and photolysis of highly halogenated PHCZs. This is the first comprehensive study to reveal the impact of printing and dyeing plant activities on PHCZs in the environment.
Subject(s)
Carbazoles , Environmental Monitoring , Water Pollutants, Chemical , Carbazoles/chemistry , Carbazoles/analysis , Water Pollutants, Chemical/analysis , China , Coloring Agents/analysis , Coloring Agents/chemistry , Rivers/chemistry , Geologic Sediments/chemistry , HalogenationABSTRACT
Biscarbazole derivative probe (6) (Z)-2-(3-(((9-heptyl-9H-carbazol-3-yl)methylene)amino)-9H-carbazol-9-yl)ethan-1-ol containing an imine group, which is a sensitive and selective fluorescence chemosensor, was designed and synthesized for the effective evaluation of Cu2+ metal ion levels. The synthesized compounds were characterized using 1H NMR, 13C NMR, FT-IR, and MALDI-TOF MS (for compound 6) spectroscopic data. The interaction model between probe 6 and Cu2+ was determined by combining fluorescence methods, 1H NMR titration, Job's plot, and theoretical calculations. For probe 6, the fluorogenic recognition of Cu2+ was investigated by fluorescence spectroscopy, and the optical changes caused by Cu2+ ions were carried out in ACN/H2O (50:50) solution at pH 7.0. Fluorescence probe 6 was found to "turn-off" its fluorescence in the presence of paramagnetic Cu2+ ions. Probe 6 was determined to have a rapid response within 40s and showed a fluorescence response to Cu2+ with a low detection limit of 0.16 µM. Additionally, in vitro anticancer activity and cell imaging studies of probe 6 against the prostate cell line (PC-3) were performed.
Subject(s)
Antineoplastic Agents , Carbazoles , Copper , Fluorescent Dyes , Spectrometry, Fluorescence , Copper/chemistry , Copper/analysis , Humans , Carbazoles/chemistry , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/pharmacology , Fluorometry/methods , Cell Line, Tumor , PC-3 CellsSubject(s)
Antifungal Agents , Carbazoles , Pyrazines , Carbazoles/chemistry , Carbazoles/pharmacology , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Pyrazines/chemistry , Pyrazines/pharmacology , Hydrogen-Ion Concentration , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacologyABSTRACT
A series of novel carbazole sulfonamide derivatives were synthesized and evaluated for antiproliferative activity. Among them, compounds 7 and 15 showed strong potency (IC50 values of 0.81-31.19 nM) against five different cancer cells including multidrug-resistant MCF7/ADR cells. Compound 15 displayed a high cancer cell selectivity (IC50(L02)/average IC50: SI = 7.7). The l-valine prodrug 7a and the phosphate prodrug 15a exerted rohust in vivo antitumor efficacies and accepted safety prolifes. Further mechanism studies revealed that 7 and 15 directly bind to the colchicine site in tubulin to block tubulin polymerization, promote microtubule fragmentation at the cellular level, and induce apoptosis with G2/M cell cycle arrest. These compounds also inhibit HEMC-1 cells migration and vascular tube formation. Additionally, compound 7 displayed a selective inhibition of Topo I. Collectively, these studies suggest that 7 and 15 represents a promising new generation of tubulin inhibitors for cancer treatment.
Subject(s)
Antineoplastic Agents , Apoptosis , Carbazoles , Cell Proliferation , Drug Screening Assays, Antitumor , Sulfonamides , Tubulin Modulators , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Carbazoles/pharmacology , Carbazoles/chemistry , Carbazoles/chemical synthesis , Structure-Activity Relationship , Sulfonamides/pharmacology , Sulfonamides/chemistry , Sulfonamides/chemical synthesis , Cell Proliferation/drug effects , Apoptosis/drug effects , Molecular Structure , Tubulin Modulators/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/chemical synthesis , Tubulin/metabolism , Dose-Response Relationship, Drug , Cell Line, Tumor , Animals , Cell Movement/drug effects , MiceABSTRACT
Overactivation of cyclic GMP-AMP synthase (cGAS) is implicated in the occurrence of many inflammatory and autoimmune diseases, and inhibition of cGAS with a specific inhibitor has been proposed as a potential therapeutic strategy. However, only a few low-potency cGAS inhibitors have been reported, and few are suitable for clinical investigation. As a continuation of our structural optimization on the reported cGAS inhibitor 6 (G140), we developed a series of spiro[carbazole-3,3'-pyrrolidine] derivatives bearing a unique 2-azaspiro[4.5]decane structural motif, among which compound 30d-S was identified with high cellular effects against cGAS. This compound showed improved plasma exposure, lower clearance, and an oral bioavailability of 35% in rats. Moreover, in the LPS-induced acute lung injury (ALI) mice model, oral administration of compound 30d-S at 30 mg/kg markedly reduced lung inflammation and alleviated histopathological changes. These results confirm that 30d-S is a new efficacious cGAS inhibitor and is worthy of further investigation.
Subject(s)
Acute Lung Injury , Carbazoles , Drug Design , Nucleotidyltransferases , Pyrrolidines , Acute Lung Injury/drug therapy , Animals , Mice , Male , Humans , Rats , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Carbazoles/chemistry , Carbazoles/therapeutic use , Carbazoles/pharmacokinetics , Pyrrolidines/pharmacology , Pyrrolidines/chemical synthesis , Pyrrolidines/chemistry , Pyrrolidines/therapeutic use , Pyrrolidines/pharmacokinetics , Nucleotidyltransferases/antagonists & inhibitors , Nucleotidyltransferases/metabolism , Lipopolysaccharides , Rats, Sprague-Dawley , Spiro Compounds/chemical synthesis , Spiro Compounds/pharmacology , Spiro Compounds/chemistry , Spiro Compounds/therapeutic use , Spiro Compounds/pharmacokinetics , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Enzyme Inhibitors/pharmacokinetics , Enzyme Inhibitors/chemistry , Structure-Activity Relationship , Molecular Docking SimulationABSTRACT
This study characterized four corrole derivatives, namely Cbz-Cor, MetCbz-Cor, PTz-Cor, and PTzEt-Cor, examining their photophysical, electrochemical, photobiological, and biomolecule-binding properties. Experimental photophysical data of absorption and emission elements correlated with a theoretical analysis obtained through time-dependent density functional theory (TD-DFT). As for the photophysical properties, we observed lower fluorescence quantum yields and discernible differences between the excited and ground states, as indicated by Stokes shift values. Natural Transition Orbit (NTO) plots presented high occupied molecular orbital - low unoccupied molecular orbital (HOMO-LUMO) densities around the tetrapyrrolic macrocycle in all examples. Our findings demonstrate that corroles maintain stability in solution and offer photostability (<20 %), predominantly in DMSO(5 %)/Tris-HCl (pH 7.4) buffer solution. Furthermore, the singlet oxygen (1O2) quantum yield and log POW values underscore their potential application in photoinactivation approaches, as these corroles serve as effective ROS generators with more lipophilic features. We also evaluated their biomolecular binding capacity towards salmon sperm DNA and human serum albumin using spectroscopic techniques and molecular docking analysis for sustenance. Concerning biomolecule interaction profiles, the corrole derivatives showed a propensity for interacting in the minor grooves of the double helix DNA due to secondary forces, which were more pronounced in site III of the human serum protein.
Subject(s)
Carbazoles , DNA , Phenothiazines , Serum Albumin, Human , DNA/chemistry , Phenothiazines/chemistry , Humans , Carbazoles/chemistry , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Porphyrins/chemistry , Animals , Protein Binding , Salmon , Molecular Docking Simulation , Singlet Oxygen/chemistry , Singlet Oxygen/metabolismABSTRACT
Neurological disorders are closely linked to the alterations in cell membrane permeability (CMP) and mitochondrial membrane potential (MMP). Changes in CMP and MMP may lead to damage and death of nerve cells, thus triggering the onset and progression of neurological diseases. Therefore, monitoring the changes of these two physiological parameters not only benefits the accurate assessment of nerve cell health status, but also enables providing key information for the diagnosis and treatment of neurological diseases. However, the simultaneous monitoring of these two cellular physiological parameters is still challenging. Herein, we design and synthesize two quinolinium-carbazole-derivated fluorescent probes (OQ and PQ). As isomers, the only difference in their chemical structures is the linking position of the carbazole unit in quinoline rings. Strikingly, such a subtle difference endows OQ and PQ with significantly different organelle-staining behaviors. PQ mainly targets at the nucleus, OQ can simultaneously stain cell membranes and mitochondria in normal cells, and performs CMP and MMP-dependent translocation from the cell membrane to mitochondria then to the nucleus, thus holding great promise as an intracellular translocation probe to image the changes of CMP and MMP. After unraveling the intrinsic mechanism of their different translocation abilities by combining experiments with molecular dynamics simulations and density functional theory calculations, we successfully used OQ to monitor the continuous changes of CMP and MMP in three neurological disease-related cell models, including oxidative stress-damaged, Parkinson's disease, and virus-infected ones. Besides providing a validated imaging tool for monitoring cellular physiological parameters, this work paves a promising route for designing intracellular translocation probes to analyze cellular physiological parameters associated with various diseases.
Subject(s)
Fluorescent Dyes , Membrane Potential, Mitochondrial , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Humans , Nervous System Diseases , Density Functional Theory , Cell Membrane Permeability , Carbazoles/chemistry , Molecular Structure , Animals , Optical ImagingABSTRACT
Conventional photosensitizers (PSs) used in photodynamic therapy (PDT) have shown preliminary success; however, they are often associated with several limitations including potential dark toxicity in healthy tissues, limited efficacy under acidic and hypoxic conditions, suboptimal fluorescence imaging capabilities, and nonspecific targeting during treatment. In response to these challenges, we developed a heavy-atom-free PS, denoted as Cz-SB, by incorporating ethyl carbazole into a thiophene-fused BODIPY core. A comprehensive investigation into the photophysical properties of Cz-SB was conducted through a synergistic approach involving experimental and computational investigations. The enhancement of intersystem crossing (kISC) and fluorescence emission (kfl) rate constants was achieved through a donor-acceptor pair-mediated charge transfer mechanism. Consequently, Cz-SB demonstrated remarkable efficiency in generating reactive oxygen species (ROS) under acidic and low-oxygen conditions, making it particularly effective for hypoxic cancer PDT. Furthermore, Cz-SB exhibited good biocompatibility, fluorescence imaging capabilities, and a high degree of localization within the mitochondria of living cells. We posit that Cz-SB holds substantial prospects as a versatile PS with innovative molecular design, representing a potential "one-for-all" solution in the realm of cancer phototheranostics.
Subject(s)
Mitochondria , Optical Imaging , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Humans , Mitochondria/metabolism , Mitochondria/drug effects , Reactive Oxygen Species/metabolism , Boron Compounds/chemistry , Boron Compounds/pharmacology , Carbazoles/chemistry , Carbazoles/pharmacology , HeLa Cells , Thiophenes/chemistry , Thiophenes/pharmacology , Cell Line, TumorABSTRACT
This study focuses on the development of regiospecific hydroarylation polyaddition of naphthalene- and carbazole-based monomers with diynes under mild reaction conditions at room temperature. A 1-pyrazole substituent serves as an appropriate directing group for a Co-catalyst to efficiently activate the C-H bonds of generally inactive six-membered aromatic hydrocarbons. The 1-pyrazole groups in 2,6-di(1-pyrazolyl)naphthalene adopt planar conformations and act as directing groups, resulting in a smooth hydroarylation reaction. In contrast, the reaction with 1,5-di(1-pyrazolyl)naphthalene do not proceed. The polyaddition reaction of 2,6-di(1-pyrazolyl)naphthalene selectively proceeds at 3,7-positions under mild reaction conditions at 30 °C, and yields corresponding poly(arylenevinylene) (PAV) with high molecular weight. This molecular design is also applicable to the hydroarylation polyaddition of carbazole; the polyaddition reaction of 9-(2-ethylhexyl)-3,6-di(1-pyrazolyl)carbazole selectively occurred at 2,7-positions. The optical and electronic properties of the synthesized compounds are evaluated. The obtained PAVs serve as an emitting material in organic light-emitting diode (OLED). This study aims to develop a Co-catalyzed hydroarylation polyaddition via C-H activation of generally inactive polyaromatic hydrocarbons (PAHs) under mild conditions.
Subject(s)
Carbazoles , Naphthalenes , Carbazoles/chemistry , Carbazoles/chemical synthesis , Catalysis , Naphthalenes/chemistry , Naphthalenes/chemical synthesis , Molecular Structure , Polyvinyls/chemistry , Polyvinyls/chemical synthesis , Cycloaddition Reaction , StereoisomerismABSTRACT
This work aimed to synthesize hydrogels by combining carbazole (Carb) with 2-hydroxy, ß-cyclodextrin (HPßCD)/polyacrylamide (PAA) hybrid complexes. The hydrogels were then evaluated for their potential use in treating infected wounds. The physicochemical structures of the preparations were evaluated using several characterization methods including FTIR, FESEM, EDX, XRD, pH sensitivity, and TGA. Moreover, In vitro release, toxicity, antibacterial activity and in vivo infected wound healing activity were evaluated. Physicochemical testing verified the effective synthesis of the preparations and the timely release of Carb. The P(AA-co-AM)/HPßCD material exhibited an open structure characterized by macroscopic voids, whereas the hydrogels displayed surfaces that were not uniform. The FTIR analysis revealed the creation of a novel polymeric hydrogel composed of HPßCD as the main polymer structure. The hydrogels exhibited good reversible swelling and recoverable deformation, with an optimal swelling ratio of 30.12 achieved at pH 7.4. The antibacterial and safety of the formulations were validated by in vitro studies. ß.Dex/PAA/Carb hydrogels have been shown to effectively expedite the healing of infected wounds by promoting the production of CD31, FGF-2, and COL1A, while reducing the levels of ROS, CD68, COX-2, and NF-κB. Overall, the combination of Carb, ß.Dex, and PAA molecules had a synergistic impact on the healing process of infected wounds.
Subject(s)
Acrylic Resins , Anti-Bacterial Agents , Carbazoles , Hydrogels , Wound Healing , beta-Cyclodextrins , Animals , Acrylic Resins/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Hydrogels/pharmacology , Mice , beta-Cyclodextrins/chemistry , Carbazoles/chemistry , Carbazoles/pharmacology , Carbazoles/chemical synthesis , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Wound Infection/drug therapy , Wound Infection/microbiology , Disease Models, Animal , Drug LiberationABSTRACT
This study evaluated the potential of isoCoQ-Carbazole, a diheterocyclic analog of isoCA-4, as an anti-tumor agent. To overcome its low aqueous solubility, liposomes were developed as a delivery system for the compound. In vitro experiments showed that loaded liposomes exhibited similar activity to the free form on multiple human tumor cell lines. In vivo experiments using a palliative intratumoral injection chemotherapy approach further demonstrated that isoCoQ-Carbazole loaded liposomes significantly reduced tumor growth in a CA-4-resistant HT29â cell model, without inducing any observable toxicity or weight loss in the treated mice. These findings suggest that liposomal isoCoQ-Carbazole may hold promise as a potential therapeutic agent for the treatment of inoperable, radiation-insensitive cancers.
Subject(s)
Antineoplastic Agents , Carbazoles , Liposomes , Solubility , Humans , Liposomes/chemistry , Carbazoles/chemistry , Carbazoles/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Animals , Mice , Cell Line, Tumor , Cell Proliferation/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Drug Screening Assays, AntitumorABSTRACT
From the 95% ethanol aqueous extract of the roots of Clausena lansium, six previously undescribed alkaloids (1, 2a, 2b, 15, 24a, 24b), a pair of prenylated phenylpropenols (26a, 26b), two coumarins (27, 28), and two undescribed sesquiterpenes (37, 38) were isolated and identified using spectroscopic and electron circular dichroism data, together with thirty-two known compounds. The absolute configurations of three alkaloids (3a, 3b, 4a) were determined for the first time. In vitro assay showed that alkaloids 7, 10, 12, 19, and furanocoumarins 34, 35 displayed inhibitory effects on the production of nitric oxide in lipopolysaccharide (LPS)-induced BV-2 microglial cells, which were stronger than that of the minocycline (positive control). RT-PCR results indicated that indizoline (7) could inhibit the expression of pro-inflammatory factors (IL-1ß, TNF-α, and IL-6) in LPS-treated BV-2 cells.
Subject(s)
Alkaloids , Clausena , Molecular Structure , Clausena/chemistry , Microglia , Lipopolysaccharides/pharmacology , Carbazoles/chemistry , Alkaloids/chemistry , Nitric OxideABSTRACT
Constructing good microphase separation structures by designing different polymer backbones and ion-conducting groups is an effective strategy for improving the ionic conductivity and chemical stability of anion exchange membranes (AEMs). In this study, a series of AEMs based on the poly(pentafluorophenylcarbazole) backbone grafted with different cationic groups are designed and prepared to construct well-defined microphase separation morphology and improve the trade-off between the properties of AEMs. Highly hydrophobic fluorinated backbone and alkyl spaces enhance phase separation and construct interconnected hydrophilic channels for anion transport. The ionic conductivity of the PC-PF-QA membrane is 123 mS cm-1 at 80 °C, and the ionic conductivity of the PC-PF-QA membrane decreased by only 6% after 960 h of immersion at 60 °C in 1 M NaOH aqueous solution. The maximum peak power density of the single cell based on PC-PF-QA is 214 mW cm-2 at 60 °C.