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Molecules (Basel, Switzerland) Mar 2024Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of...
Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine-azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320-420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine-isoxazole hybrids linked at the C9-C3 or C2-C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, -xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl -butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine-azirine, acridine-isoxazole, and acridane-isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4).
PubMed: 38611817
DOI: 10.3390/molecules29071538 -
Angewandte Chemie (International Ed. in... Jun 2024Developing candidate materials which possess the ability of both selective detection and efficient capture of precious metal gold is highly desirable for environment and...
Developing candidate materials which possess the ability of both selective detection and efficient capture of precious metal gold is highly desirable for environment and economy. However, most of reported materials only focus on single function, which seriously restricts their practical application as probes or adsorbents. Herein, a two dimensional (2D) acridine-based covalent organic framework (TpDa-COF) is prepared via the linkage of imine bonds for gold detection and adsorption. The synthesized COF can achieve both fluorescence and colorimetric dual sensing for Au in a low concentration range (0.1-1.5 ppm) with the limit of detection (LOD) of 0.036 ppm. Impressively, the selectivity of TpDa-COF for the detection of Au is admirable (Fe, Fe and Cu for negligible influence on its fluorescence). In addition, TpDa-COF exhibits ultrahigh adsorption capacity of 982.5 mg ⋅ g for gold at pH=4, which is attributed the synergistic effect of both selective coordination and reductive process of Au(III) to Au(0). Meanwhile, both positive entropy change (ΔS=76.07 J ⋅ mol ⋅ K) and high distribution coefficient (K=12484.8 mL ⋅ g) confirm the good affinity between TpDa-COF framework and gold. This work gives us a new insight to prepare COF with pyridine nitrogen sites for gold detection and adsorption.
PubMed: 38606878
DOI: 10.1002/anie.202402205 -
Journal of Biochemical and Molecular... Apr 2024In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We...
In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two-step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a-e and 4a-e using a Suzuki-Miyaura cross-coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5-Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.
Topics: Female; Humans; Tacrine; Antifungal Agents; Anticonvulsants; Anti-Bacterial Agents; Enzyme Inhibitors; Antineoplastic Agents; Neoplasms; Structure-Activity Relationship; Molecular Structure
PubMed: 38591869
DOI: 10.1002/jbt.23706 -
Journal of Fluorescence Apr 2024This research investigates the excimerisation of acriflavine dye in ethylene glycol and glycerol solvents. Acriflavine, a member of the acridine dye family, exhibits...
This research investigates the excimerisation of acriflavine dye in ethylene glycol and glycerol solvents. Acriflavine, a member of the acridine dye family, exhibits unique fluorescence properties with applications in various fields, including cellular nucleus observation, nucleic acid analysis, and dye laser active media etc. The study explores the impact of solvent and concentration on acriflavine's emission properties, with a focus on excimer formation, which can influence its suitability as a dye laser active medium. UV-Visible absorption spectroscopy reveals concentration-dependent absorption profiles, with distinctive monomer bands. Steady-state fluorescence studies demonstrate the emergence of red-shifted excimer fluorescence bands as concentrations increase in both solvents. Temperature-dependent fluorescence studies reveal the dynamics of excimer formation, suggesting dynamic diffusion as the excimerisation mechanism. Time-resolved fluorescence spectroscopy confirms the singlet character of both monomer and excimer states, providing insights into the excimerisation process. Critical concentration values are determined, representing the equilibrium between monomeric and excimeric forms. The study also explores pH-induced spectral shifts, highlighting the influence of acidity on fluorescence properties. Overall, this research deepens our understanding of acriflavine's excimerisation in ethylene glycol and glycerol, offering insights that can enhance its diverse applications, especially in laser technologies.
PubMed: 38587712
DOI: 10.1007/s10895-024-03686-w -
Organic Letters Apr 2024A concept for the dual use of acridine and tetrabutylammonium decatungstate photocatalysts in the reactions of carboxylic acids is proposed. Imines generated in situ...
A concept for the dual use of acridine and tetrabutylammonium decatungstate photocatalysts in the reactions of carboxylic acids is proposed. Imines generated in situ from aldehydes and -methoxyaniline, as well as other azomethines, were used as radical acceptors. The role of the decatungstate is believed to facilitate the turnover of the acridine photocatalyst by means of hydrogen atom transfer.
PubMed: 38587457
DOI: 10.1021/acs.orglett.4c00778 -
Biochemical and Biophysical Research... May 2024P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug...
P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. This mechanism is particularly problematic in cancer cells, where it diminishes the therapeutic efficacy of anticancer drugs. P-gp inhibitors, such as elacridar, have been developed to circumvent the decrease in drug efficacy due to P-gp efflux. An earlier study reported the cryo-EM structure of human P-gp-Fab (MRK-16) complex bound by two elacridar molecules, at a resolution of 3.6 Å. In this study, we have obtained a higher resolution (2.5 Å) structure of the P-gp- Fab (UIC2) complex bound by three elacridar molecules. This finding, which exposes a larger space for compound-binding sites than previously acknowledged, has significant implications for the development of more selective inhibitors and enhances our understanding of the compound recognition mechanism of P-gp.
Topics: Humans; Acridines; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cryoelectron Microscopy; Tetrahydroisoquinolines
PubMed: 38579618
DOI: 10.1016/j.bbrc.2024.149855 -
Journal of Hazardous Materials May 2024Carbazole (CBZ) and acridine (ACR) are polycyclic aromatic nitrogen heterocycles (PANHs) widely found in combined contaminated soils, while investigations on...
Carbazole (CBZ) and acridine (ACR) are polycyclic aromatic nitrogen heterocycles (PANHs) widely found in combined contaminated soils, while investigations on organic-organic interactions have been very limited. In this study, batch experiments were carried out on five soils with different properties, taking CBZ as a representative of PANHs and ACR as a co-existing contaminant. The adsorption isotherms of CBZ (50-1000 μg/L) were nonlinear. Soil organic matter (SOM) and cation exchange capacity (CEC) showed positive correlations with CBZ adsorption-desorption coefficients. The adsorption mechanisms of CBZ involved hydrogen bonding, π-π interaction, and cation-π bonding. Different concentrations of ACR had varying effects on CBZ. The adsorption of CBZ was inhibited with 250 μg/L ACR. The cooperative adsorption was observed on three soils with increasing ACR concentration (1000 μg/L) and led to more pronounced nonlinear isotherms. The S-shaped isotherms of ACR indicated that ACR was adsorbed to the soil surface in a perpendicular configuration. New adsorption sites were created allowing for increased CBZ adsorption through π-π interaction with ACR. Therefore, variations in soil properties and potential impacts of co-existing contaminants should be well considered when assessing the combined pollution of site soil. This will contribute to a more accurate estimation of environmental and health risks.
PubMed: 38579583
DOI: 10.1016/j.jhazmat.2024.134205 -
The Journal of Physical Chemistry. A Apr 2024In our experiment, a trace amount of an organic molecule (M = 1-phenalen-1-one, 9-fluorenone, pyridine, or acridine) was seeded into a gas mix consisting of 3% O with a...
In our experiment, a trace amount of an organic molecule (M = 1-phenalen-1-one, 9-fluorenone, pyridine, or acridine) was seeded into a gas mix consisting of 3% O with a rare gas buffer (He or Ar) and then supersonically expanded. We excited the resulting molecular beam with ultraviolet light at either 355 nm (1-phenalen-1-one, 9-fluorenone, or acridine) or 266 nm (pyridine) and used resonance enhanced multiphoton ionization (REMPI) spectroscopy to probe for the formation of O in the a-Δ state, O. For all systems, the REMPI spectra demonstrate that ultraviolet excitation results in the formation of O and the oxygen product is confirmed to be in the ground vibrational state and with an effective rotational temperature below 80 K. We then recorded the velocity map ion image of the O product. From the ion images, we determined the center-of-mass translational energy distribution, (), assuming photodissociation of a bimolecular M-O complex. We also report results from electronic structure calculations that allow for a determination of the M-O ground state binding energy. We use the complex binding energy, the energy to form O, and the adiabatic triplet energy for each organic molecule to determine the available energy following photodissociation. For dissociation of a bimolecular complex, this available energy may be partitioned into either center-of-mass recoil or internal degrees of freedom of the organic moiety. We use the available energy to generate a Prior distribution, which predicts statistical energy partitioning during dissociation. For low available energies, less than 0.2 eV, we find that the statistical prediction is in reasonable agreement with the experimental observations. However, at higher available energies, the experimental distribution is biased to lower center-of-mass kinetic energies compared with the statistical prediction, which suggests the complex undergoes vibrational predissociation.
PubMed: 38579334
DOI: 10.1021/acs.jpca.4c00143 -
Journal of the American Chemical Society Apr 2024Dinitrogen (N) activation and functionalization through N-N bond cleavage and N-C bond formation are of great interest and importance but remain highly challenging. We...
Dinitrogen (N) activation and functionalization through N-N bond cleavage and N-C bond formation are of great interest and importance but remain highly challenging. We report here for the first time N cleavage and selective multicoupling with isocyanides in a dititanium dihydride framework. The reaction of a dinitrogen dititanium dihydride complex [{(PNP)Ti}(μ-η:η-N)(μ-H)] () with an excess (four or more equivalents) of -methoxyphenyl isocyanide at room temperature gave a novel amidoamidinatoguanidinate complex [(PNP)Ti{NC(═NR)NC(═NR)CHNR}Ti(PNP)(CNR)] (, PNP = 4,5-bis(diisopropylphosphino)-2,7,9,9-tetramethyl-9-acridin-10-ide; R = -MeOCH) through N splitting and coupling with three isocyanide molecules. When 1 equiv of -methoxyphenyl isocyanide was used to react with at -30 °C, the hydrogenation of the isocyanide unit by the two hydride ligands in took place, affording an amidomethylene-bridged dititanium dinitrogen complex [{(PNP)Ti}(μ-η:η-N){μ-η:η-CHN(-MeOCH)}] (), which upon reaction with another equivalent of -methoxyphenyl isocyanide at room temperature gave an amidomethylene/nitrido/carbodiimido complex [(PNP)Ti(N═C═NR)(μ-N)(μ-η:η-CHNR)Ti(PNP)] () through N cleavage and N═C bond formation. Further reaction of with 1 equiv of -methoxyphenyl isocyanide led to an unprecedented four-component (carbodiimido, nitrido, isocyanide, and amidomethylene) coupling, yielding an amidoamidinatoguanidinate complex [{(PNP)Ti}{NC(═NR)NC(═NR)CHNR}] (), which on reaction with another equivalent of -methoxyphenyl isocyanide afforded the isocyanide-coordinated analogue . The reaction of with 2-naphthyl isocyanide also took place in a similar multicoupling fashion. Moreover, the cross-coupling reactions of the -methoxyphenyl isocyanide-derived amidomethylene/nitrido/carbodiimido complex with 2-naphthyl isocyanide, cyclohexyl isocyanide, and -butyl isocyanide were also achieved, which afforded the corresponding amidoamidinatoguanidinate products consisting of two different isocyanides. Density functional theory (DFT) calculations further elucidated the mechanistic details.
PubMed: 38578866
DOI: 10.1021/jacs.4c02905 -
Methods in Molecular Biology (Clifton,... Apr 2024Microbial dysbiosis is an important trigger in the development of oral diseases. Oral keratinocytes or gingival epithelial cells (GECs) offer protection against various...
Microbial dysbiosis is an important trigger in the development of oral diseases. Oral keratinocytes or gingival epithelial cells (GECs) offer protection against various microbial insults. Recent studies suggest that GECs expressed higher level of bitter taste receptor 14 (T2R14) compared to other taste receptors and toll-like receptors and act as innate immune sentinels. Macroautophagy or autophagy is a cellular conserved process involved in the regulation of host innate immune responses against microbial infection. Here, we describe a robust method for evaluation of T2R14-dependent autophagy flux in GECs. Autophagy flux was detected using Western blot analysis in GECs and further was confirmed using Acridine Orange-dependent flow cytometry analysis.
PubMed: 38578576
DOI: 10.1007/7651_2024_531