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1.
Chem Biol Drug Des ; 104(3): e14623, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39279715

ABSTRACT

Hepatocellular carcinoma (HCC) is a significant global health concern. However, there are limited effective treatments available for it. The use of natural products in the management and treatment of HCC is gaining more attention. Baicalein is a flavonoid compound that has been reported to have antitumor activities in HCC. However, the direct binding targets of baicalein are still unknown. Therefore, we used the DNA-programmed affinity labeling method to identify the target of baicalein and validated its function in HCC cells. We set blank and competitive DNA probes as negative controls. The results showed that baicalein had 136 binding targets, of which 13 targets were differently expressed in HCC tissues. The enriched cellular process of these targets was apoptosis, which involved MAPK9. We tested the binding affinity of baicalein with MAPK9 as 89.7 nM (Kd) by surface plasmon resonance and analyzed the binding sites by virtual docking. Notably, the binding of baicalein with MAPK9 increased the protein levels of MAPK9 itself and the related downstream apoptosis signaling, triggering the apoptosis of HCC cells. However, the inhibitor of MAPK9, SP600125, blocked the baicalein-induced apoptosis, and the amounts of MAPK9 and downstream molecules were also decreased, indicating that baicalein acted through MAPK9 to induce apoptosis of HCC cells. In conclusion, we used the DNA-programmed affinity labeling method to identify the direct-binding target MAPK9 of baicalein and validated its function in baicalein-induced apoptosis of HCC cells, which would be helpful to understand and use baicalein in HCC therapy.


Subject(s)
Apoptosis , Carcinoma, Hepatocellular , Flavanones , Liver Neoplasms , Molecular Docking Simulation , Humans , Anthracenes/pharmacology , Anthracenes/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Binding Sites , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Flavanones/pharmacology , Flavanones/chemistry , Flavanones/metabolism , Hep G2 Cells , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Protein Binding
2.
Int J Mol Sci ; 25(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39337451

ABSTRACT

Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible light, which transform into chemical compounds harmful to health. Manufacturers often include information on the prohibition of exposure to sunlight on the packaging, but consumers often do not read the product leaflet. The solution to this problem may be the addition of silver particles to preparations. In the presented article, we proposed the use of silver nanoparticles to reduce the photobleaching and photoreaction of fluorophore, while increasing the fluorescence intensity. For our research, we used a compound that is particularly sensitive to radiation: hypericin.


Subject(s)
Anthracenes , Metal Nanoparticles , Perylene , Silver , Silver/chemistry , Perylene/analogs & derivatives , Perylene/chemistry , Metal Nanoparticles/chemistry , Anthracenes/chemistry , Fluorescent Dyes/chemistry , Photobleaching , Light
3.
J Biosci Bioeng ; 138(4): 283-289, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39097441

ABSTRACT

GroEL, a chaperone protein responsible for peptide and denatured protein folding, undergoes substantial conformational changes driven by ATP binding and hydrolysis during folding. Utilizing these conformational changes, we demonstrated the GroEL-mediated regioselective photocyclodimerization of 2-anthracenecarboxylic acid (AC) using ATP hydrolysis as an external stimulus. We designed and prepared an optimal GroEL mutant to employ in a docking simulation that has been actively used in recent years. Based on the large difference in the motif of hydrogen bonds between AC and GroEL mutant compared with the wild-type, we predicted that GroELMEL, in which the 307‒309th amino acid residues were mutated to Ala, could alter the orientation of bound AC in GroEL. The GroELMEL-mediated photocyclodimerization of AC can be used for regioselective inversion upon ATP addition to a moderate extent.


Subject(s)
Adenosine Triphosphate , Anthracenes , Chaperonin 60 , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/chemistry , Hydrolysis , Anthracenes/chemistry , Anthracenes/metabolism , Chaperonin 60/chemistry , Chaperonin 60/genetics , Chaperonin 60/metabolism , Molecular Docking Simulation , Protein Conformation , Mutation , Hydrogen Bonding , Protein Folding , Carboxylic Acids
4.
Biochemistry ; 63(17): 2111-2130, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39140188

ABSTRACT

In previous work, we reported on iridium(III) (Ir(III)) complex-peptide hybrids as amphiphilic conjugates (IPH-ACs) and triptycene-peptide hybrids as amphiphilic conjugates (TPH-ACs) and found that these hybrid compounds containing three cationic KK(K)GG peptide units through C6-C8 alkyl linkers induce paraptosis II, which is one of the nonapoptotic programmed cell death (PCD) types in Jurkat cells and different from previously reported paraptosis. The details of that study revealed that the paraptosis II induced by IPH-ACs (and TPH-ACs) proceeds via a membrane fusion or tethering of the endoplasmic reticulum (ER) and mitochondria, and Ca2+ transfer from the ER to mitochondria, which results in a loss of mitochondrial membrane potential (ΔΨm) in Jurkat cells. However, the detailed mechanistic studies of paraptosis II have been conducted only in Jurkat cells. In the present work, we decided to conduct mechanistic studies of paraptosis II in HeLa-S3 and A549 cells as well as in Jurkat cells to study the general mechanism of paraptosis II. Simultaneously, we designed and synthesized new TPH-ACs functionalized with peptides that contain cyclohexylalanine, which had been reported to enhance the localization of peptides to mitochondria. We found that TPH-ACs containing cyclohexylalanine promote paraptosis II processes in Jurkat, HeLa-S3 and A549 cells. The results of the experiments using fluorescence Ca2+ probes in mitochondria and cytosol, fluorescence staining agents of mitochondria and the ER, and inhibitors of paraptosis II suggest that TPH-ACs induce Ca2+ increase in mitochondria and the membrane fusion between the ER and mitochondria almost simultaneously, suggesting that our previous hypothesis on the mechanism of paraptosis II should be revised.


Subject(s)
Mitochondria , Humans , Jurkat Cells , HeLa Cells , Mitochondria/metabolism , Mitochondria/drug effects , Peptides/chemistry , Peptides/pharmacology , Peptides/metabolism , Calcium/metabolism , Membrane Potential, Mitochondrial/drug effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/drug effects , Anthracenes/chemistry , Anthracenes/pharmacology , A549 Cells , Iridium/chemistry , Iridium/pharmacology , Cell Death/drug effects , Apoptosis/drug effects , Paraptosis
5.
ACS Appl Mater Interfaces ; 16(33): 43416-43429, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39121233

ABSTRACT

The lipopolyplex, a multicomponent nonviral gene carrier, generally demonstrates superior colloidal stability, reduced cytotoxicity, and high transfection efficiency. In this study, a new concept, photochemical reaction-induced transfection, using photosensitizer (PS)-loaded lipopolyplexes was applied, which led to enhanced transfection and cytotoxic effects by photoexcitation of the photosensitizer. Hypericin, a hydrophobic photosensitizer, was encapsulated in the lipid bilayer of liposomes. The preformed nanosized hypericin liposomes enclosed the linear polyethylenimine (lPEI)/pDNA polyplexes, resulting in the formation of hypericin lipopolyplexes (Hy-LPP). The diameters of Hy-LPP containing 50 nM hypericin and 0.25 µg of pDNA were 185.6 ± 7.74 nm and 230.2 ± 4.60 nm, respectively, measured by dynamic light scattering (DLS) and atomic force microscopy (AFM). Gel electrophoresis confirmed the encapsulation of hypericin and pDNA in lipopolyplexes. Furthermore, in vitro irradiation of intracellular Hy-LPP at radiant exposures of 200, 600, and 1000 mJ/cm2 was evaluated. It demonstrated 60- to 75-fold higher in vitro luciferase expression than that in nonirradiated cells. The lactate dehydrogenase (LDH) assay supported that reduced transfection was a consequence of photocytotoxicity. The developed photosensitizer-loaded lipopolyplexes improved the transfection efficiency of an exogenous gene or induced photocytotoxicity; however, the frontier lies in the applied photochemical dose. The light-triggered photoexcitation of intracellular hypericin resulted in the generation of reactive oxygen species (ROS), leading to photoselective transfection in HepG2 cells. It was concluded that the two codelivered therapeutics resulted in enhanced transfection and a photodynamic effect by tuning the applied photochemical dose.


Subject(s)
Anthracenes , Carcinoma, Hepatocellular , Liposomes , Liver Neoplasms , Perylene , Photosensitizing Agents , Transfection , Perylene/chemistry , Perylene/analogs & derivatives , Perylene/pharmacology , Anthracenes/chemistry , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Transfection/methods , Liposomes/chemistry , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/pathology , Hep G2 Cells , DNA/chemistry , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Plasmids/chemistry , Cell Survival/drug effects
6.
J Chromatogr A ; 1732: 465210, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39098100

ABSTRACT

Various crossover phenomena are immanent to supercritical fluids due to multidirectional temperature effects in highly compressible supercritical fluid media. Solubility crossover, i.e. controversial effect of temperature on solubility at different pressures, is probably the most well-known among them. A curious discrepancy in upper crossover pressure values between solubility in supercritical carbon dioxide and retention in supercritical fluid chromatography with pure CO2 as an eluent was unexpectedly observed for several non-polar compounds on different stationary phases. In some cases, retention crossover was found to happen at pressures almost twice as high as pressures for solubility crossover for the same compound. Retention data for three solutes with known solubility crossovers: anthracene, benzoic acid and vanillin, were collected at different pressures and temperatures for several stationary phases. The existence of upper retention crossovers, i.e. such pressure values beyond which temperature increase starts decreasing retention, were registered for all solute-sorbent combinations. Using known thermodynamic models of temperature effect on retention in supercritical fluid chromatography and on solubility in supercritical carbon dioxide, possible reasoning for the observed discrepancies is discussed. Major contribution of the balance between adsorption and partition retention mechanisms in defining retention crossover values is hypothesized.


Subject(s)
Carbon Dioxide , Chromatography, Supercritical Fluid , Pressure , Solubility , Temperature , Chromatography, Supercritical Fluid/methods , Carbon Dioxide/chemistry , Anthracenes/chemistry , Benzoic Acid/chemistry , Thermodynamics , Benzaldehydes/chemistry , Adsorption
7.
Dalton Trans ; 53(29): 12152-12161, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38989958

ABSTRACT

Laccases (EC 1.10.3.2) are multicopper oxidases with the capability to oxidize diverse phenolic and non-phenolic substrates. While the molecular mechanism of their activity towards phenolic substrates is well-established, their reactivity towards non-phenolic substrates, such as polycyclic aromatic hydrocarbons (PAHs), remains unclear. To elucidate the oxidation mechanism of PAHs, particularly the activation mechanism of the sp2 aromatic C-H bond, we conducted a density functional theory investigation on the oxidation of two PAHs (anthracene and benzo[a]pyrene) using an extensive model of the T1 copper catalytic site of the fungal laccase from Trametes versicolor.


Subject(s)
Anthracenes , Benzo(a)pyrene , Copper , Laccase , Oxidation-Reduction , Laccase/metabolism , Laccase/chemistry , Anthracenes/chemistry , Anthracenes/metabolism , Copper/chemistry , Copper/metabolism , Benzo(a)pyrene/metabolism , Benzo(a)pyrene/chemistry , Density Functional Theory , Models, Molecular , Polyporaceae/enzymology , Catalytic Domain , Polyporales/enzymology , Polyporales/metabolism , Trametes/enzymology
8.
J Mater Chem B ; 12(33): 8099-8106, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39075949

ABSTRACT

Stimuli-responsive supramolecular chemotherapy, particularly in response to cancer biomarkers, has emerged as a promising strategy to overcome the limitations associated with traditional chemotherapy. Spermine (SPM) is known to be overexpressed in certain cancers. In this study, we introduced a novel supramolecular chemotherapy system triggered by SPM. The system featured pyridine salts of a diphenylanthracene derivative (PyEn) and a complementary water-soluble pillar[5]arene (WP5C5) with long alkyl chains. The diphenylanthracene unit of PyEn is effectively encapsulated within the long alkyl chains of WP5C5, resulting in a substantial reduction in the cytotoxicity of PyEn towards normal cells. The therapeutic effect of PyEn is selectively triggered intracellularly through SPM, leading to the endosomal release of PyEn and concurrent in situ cytotoxicity. This supramolecular chemotherapy system exhibits notable tumor inhibition against SPM-overexpressed cancers with reduced side effects on normal tissues. The supramolecular strategy for intracellular activation provides a novel tool with potential applications in chemotherapeutic interventions, offering enhanced selectivity and reduced cytotoxicity to normal cells.


Subject(s)
Anthracenes , Antineoplastic Agents , Calixarenes , Quaternary Ammonium Compounds , Solubility , Spermine , Water , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Calixarenes/chemistry , Calixarenes/pharmacology , Water/chemistry , Anthracenes/chemistry , Spermine/chemistry , Spermine/pharmacology , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Animals , Drug Screening Assays, Antitumor , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacology , Surface-Active Agents/chemical synthesis , Cell Survival/drug effects , Mice , Molecular Structure , Cell Proliferation/drug effects , Particle Size
9.
Anal Methods ; 16(30): 5263-5271, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39015041

ABSTRACT

A fluorescent molecule, pyridine-coupled bis-anthracene (PBA), has been developed for the selective fluorescence turn-on detection of Cu2+. Interestingly, the ligand PBA also exhibited a red-shifted ratiometric fluorescence response in the presence of water. Thus, a ratiometric water sensor has been utilized as a selective fluorescence turn-on sensor for Cu2+, achieving a 10-fold enhancement in the fluorescence and quantum yield at 446 nm, with a lower detection limit of 0.358 µM and a binding constant of 1.3 × 106 M-1. For practical applications, sensor PBA can be used to detect Cu2+ in various types of soils like clay soil, field soil and sand. The interaction of the PBA-Cu(II) complex with transport proteins like bovine serum albumin (BSA) and ct-DNA has been investigated through fluorescence titration experiments. Additionally, the structural optimization of PBA and the PBA-Cu(II) complex has been demonstrated by DFT, and the interaction of the PBA-Cu(II) complex with BSA and ct-DNA has been analyzed using theoretical docking studies.


Subject(s)
Copper , DNA , Molecular Docking Simulation , Serum Albumin, Bovine , Spectrometry, Fluorescence , Water , Serum Albumin, Bovine/chemistry , Copper/chemistry , Copper/analysis , DNA/chemistry , Spectrometry, Fluorescence/methods , Cattle , Animals , Water/chemistry , Fluorescent Dyes/chemistry , Anthracenes/chemistry , Limit of Detection , Pyridines/chemistry , Fluorescence , Coordination Complexes/chemistry
10.
J Photochem Photobiol B ; 258: 112977, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38991294

ABSTRACT

To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.


Subject(s)
Alginates , Anthracenes , Nanoparticles , Perylene , Silicon Dioxide , Tirapazamine , Tumor Microenvironment , Silicon Dioxide/chemistry , Tumor Microenvironment/drug effects , Alginates/chemistry , Animals , Humans , Tirapazamine/chemistry , Tirapazamine/pharmacology , Nanoparticles/chemistry , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Mice , Anthracenes/chemistry , Cell Line, Tumor , Photochemotherapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Drug Delivery Systems , Drug Liberation , Porosity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Drug Synergism , Nanoparticle Drug Delivery System/chemistry
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124565, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-38875925

ABSTRACT

Endogenous CO acts as an important messenger for signal transduction and therapeutic effect in the human body. Fluorescent imaging appears to be a promising method for endogenous CO recognition, but traditional luminescent probes based on Pd-complexes suffered from defects of high cost. In this work, four anthracene-derived dyes having an = N-N = group were synthesized for Cu2+-assisted CO sensing. Their molecular structure, photophysical performance and spectral response to Cu2+ and CO were analyzed in detail. The optimal probe showed good selectivity and quenching effect to Cu2+, with PLQY (photoluminescence quantum yield) decreased from 0.33 to 0.04. The quenching mechanism was found as a static quenching mechanism by forming a non-fluorescent complex with Cu2+ (stoichiometric ratio = 1:1), as revealed by single crystal, EPR (electron paramagnetic resonance), and XPS (X-ray photoelectron spectroscopy) analysis. Such quenching effect could be reversed by CO, showing recovered fluorescence, with PLQY recovered to 0.32 within 328 s. Discussion on cellular endogenous CO imaging was included as well.


Subject(s)
Anthracenes , Copper , Fluorescent Dyes , Anthracenes/chemistry , Copper/chemistry , Copper/analysis , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Spectrometry, Fluorescence , Photoelectron Spectroscopy , Electron Spin Resonance Spectroscopy
12.
J Colloid Interface Sci ; 674: 186-193, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-38925064

ABSTRACT

The effective measurement of temperature in living systems at the nano and microscopic scales continues to be a challenge to this day. Here, we study the use of 2-(anthracen-2-yl)-1,3-diisopropylguanidine, 1, as a nanothermometer based on fluorescence lifetime measurements and its bioimaging applications. In aqueous solution, 1 is shown in aggregated form and the equilibrium between the two main aggregate types (T-shaped and π-π) is highly sensitive to the temperature. The heating of the medium shifts the equilibrium toward the formation of highly emissive T-shaped aggregates. This species shows a high fluorescence emission and a long lifetime in comparison with the π-π aggregates and the freé monomer. A linear relationship between the fluorescence lifetime and the temperature both in aqueous solution and in a synthetic intracellular buffer was found. Fluorescence lifetime imaging microscopy (FLIM) also showed a linear relationship between lifetime and temperature with an excellent sensitivity in MCF7 breast cancer cells, which opens the door for its potential use as FLIM nanothermometer in the biomedical field.


Subject(s)
Anthracenes , Humans , Anthracenes/chemistry , MCF-7 Cells , Microscopy, Fluorescence , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Thermometers , Fluorescence , Temperature , Optical Imaging
13.
J Biomater Sci Polym Ed ; 35(12): 1795-1818, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38801735

ABSTRACT

In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 µg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field.


Subject(s)
Anthracenes , Anti-Bacterial Agents , Disulfides , Drug Carriers , Escherichia coli , Perylene , Photochemotherapy , Polyethylene Glycols , Reactive Oxygen Species , Silicon Dioxide , Staphylococcus aureus , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Anthracenes/chemistry , Polyethylene Glycols/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Silicon Dioxide/chemistry , Staphylococcus aureus/drug effects , Porosity , Reactive Oxygen Species/metabolism , Drug Carriers/chemistry , Disulfides/chemistry , Hemolysis/drug effects , Humans , Animals , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry
14.
Biosens Bioelectron ; 258: 116342, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38705071

ABSTRACT

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.


Subject(s)
Anthracenes , Biosensing Techniques , Circular Dichroism , Nanotubes , Nucleosides , Anthracenes/chemistry , Nanotubes/chemistry , Biosensing Techniques/methods , Nucleosides/chemistry , Water/chemistry , Stereoisomerism
15.
Chemistry ; 30(38): e202400941, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38700909

ABSTRACT

Anthracene carboximides (ACIs) conjugated with gluco-, galacto- and mannopyranosides are synthesized, by glycosylation of N-hydroxyethylanthracene carboximide acceptor with glycosyl donors. Glycoconjugation of anthracene carboximide increases the aq. solubility by more than 3-fold. The glycoconjugates display red-shifted absorption and emission, as compared to anthracene. Large Stokes shift (λabs/λem=445/525 nm) and high fluorescence quantum yields (Φ) of 0.86 and 0.5 occur in THF and water, respectively. The ACI-glycosides undergo facile photodimerization in aqueous solutions, leading to the formation of the head-to-tail dimer, as a mixture of syn and anti-isomers. Solution phase and solid-state characterizations by dynamic light scattering (DLS), microscopic imaging by atomic force (AFM) and transmission electron (TEM) microscopies reveal self-assembled vesicle structures of ACI glycosides. These self-assembled structures act as multivalent glycoclusters for ligand-specific lectin binding, as evidenced by the binding of Man-ACI to Con A, by fluorescence and turbidity assays. The conjugates do not show cellular cytotoxicity (IC50) till concentrations of 50 µM with HeLa and HepG2 cell lines and are cell-permeable, showing strong fluorescence inside the cells. These properties enable the glycoconjugates to be used in cell imaging. The non-selective cellular uptake of the glycoconjugates suggests a passive diffusion through the membrane.


Subject(s)
Anthracenes , Glycoconjugates , Anthracenes/chemistry , Humans , Ligands , Hep G2 Cells , HeLa Cells , Glycoconjugates/chemistry , Carbohydrates/chemistry , Glycosylation , Glycosides/chemistry , Imides/chemistry
16.
Macromol Rapid Commun ; 45(14): e2400087, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38688322

ABSTRACT

The collapse or folding of an individual polymer chain into a nanoscale particle gives rise to single-chain nanoparticles (SCNPs), which share a soft nature with biological protein particles. The precise control of their properties, including morphology, internal structure, size, and deformability, are a long-standing and challenging pursuit. Herein, a new strategy based on amphiphilic alternating copolymers for producing SCNPs with ultrasmall size and uniform structure is presented. SCNPs are obtained by folding the designed alternating copolymer in N,N-dimethylformamide (DMF) and fixing it through a photocatalyzed cycloaddition reaction of anthracene units. Molecular dynamics simulation confirms the solvophilic outer corona and solvophobic inner core structure of SCNPs. Furthermore, by adjusting the length of PEG units, precise control over the mean size of SCNPs is achieved within the range of 2.8 to 3.9 nm. These findings highlight a new synthetic strategy that enables enhanced control over morphology and internal structure while achieving ultrasmall and uniform size for SCNPs.


Subject(s)
Molecular Dynamics Simulation , Nanoparticles , Particle Size , Polymers , Nanoparticles/chemistry , Polymers/chemistry , Surface-Active Agents/chemistry , Molecular Structure , Anthracenes/chemistry
17.
J Hazard Mater ; 471: 134386, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38663297

ABSTRACT

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.


Subject(s)
Anthracenes , Keratinocytes , Photolysis , Skin , Anthracenes/toxicity , Anthracenes/chemistry , Humans , Keratinocytes/drug effects , Keratinocytes/radiation effects , Animals , Skin/drug effects , Skin/radiation effects , Skin/metabolism , Cell Survival/drug effects , Mice , Cell Movement/drug effects , Sunlight , Mice, Hairless , Anthraquinones/toxicity , Anthraquinones/chemistry , Cell Differentiation/drug effects
18.
Small ; 20(31): e2310608, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38461532

ABSTRACT

Depression is a significant global health concern that remains inadequately treated due to the limited effectiveness of conventional drug therapies. One potential therapeutic agent, hypericin (HYP), is identified as an effective natural antidepressant. However, its poor water solubility, low bioavailability, and limited ability to penetrate the brain parenchyma have hindered its clinical application. To address these shortcomings and enhance the therapeutic efficacy of HYP, it is loaded onto black phosphorus nanosheets (BP) modified with the neural cell-targeting peptide RVG29 to synthesize a nanoplatform named BP-RVG29@HYP (BRH). This platform served as a nanocarrier for HYP and integrated the advantages of BP with advanced delivery methods and precise targeting strategies. Under the influence of 808 nm near-infrared irradiation (NIR), BRH effectively traversed an in vitro BBB model. In vivo experiments validated these findings, demonstrating that treatment with BRH significantly alleviated depressive-like behaviors and oxidative stress in mice. Importantly, BRH exhibited an excellent safety profile, causing minimal adverse effects, which highlighted its potential as a promising therapeutic agent. In brief, this novel nanocarrier holds great promise in the development of antidepressant drugs and can create new avenues for the treatment of depression.


Subject(s)
Anthracenes , Brain , Depression , Perylene , Phosphorus , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Animals , Anthracenes/chemistry , Phosphorus/chemistry , Brain/metabolism , Brain/drug effects , Depression/drug therapy , Mice , Drug Delivery Systems , Blood-Brain Barrier/metabolism , Nanoparticles/chemistry , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/chemistry , Oxidative Stress/drug effects
19.
Macromol Rapid Commun ; 45(10): e2300658, 2024 May.
Article in English | MEDLINE | ID: mdl-38362957

ABSTRACT

The problem of plastic waste in the environment calls for the development of new polymeric materials designed specifically for easy recycling at the end of their life cycle. Herein, a green polymer system comprising a series of necklace-shaped polydimethylsiloxanes bearing anthracene dimer units is developed. The polymers have low environmental impact and are easily recycled. Further, their flexibility and glass transition temperatures are easy to control. These necklace-shaped inorganic polymers are synthesized by photopolymerizing (dimerizing) anthracene-terminated oligo-dimethylsiloxane monomers. A key achievement of the present work is the successful chemical recovery of the monomers from the polymers through thermal depolymerization, enabling monomer-polymer recycling. By applying equilibrium polymerization with base catalysts, monomers with a controlled distributed chain length are synthesized from monomers with a constant chain length. The necklace-shaped polymers synthesized from these randomized monomers have amorphous structures and readily form transparent films. It is possible to modulate the thermal and mechanical properties of the polymers by controlling the average chain length of the polydimethylsiloxane between the anthracene dimers. This investigation presents a method for the synthesis and cyclic utilization of polymer materials with a wide range of applications, including plastics and elastomers.


Subject(s)
Anthracenes , Dimethylpolysiloxanes , Polymerization , Anthracenes/chemistry , Dimethylpolysiloxanes/chemistry , Dimerization , Molecular Structure , Polymers/chemistry , Polymers/chemical synthesis , Recycling
20.
Environ Res ; 252(Pt 1): 118454, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38387488

ABSTRACT

The oncogenic and genetic properties of anthracene, a member of the polycyclic aromatic hydrocarbons (PAHs) family, pose a significant health threat to humans. This study aims to investigate the photocatalytic decomposition of anthracene under various conditions, such as different concentrations of PAHs, varying amounts of NiO (nickel oxide) nanoparticles, and different pH levels under ultraviolet light and sunlight. The synthesized NiO nanoparticles showed surface plasma resonance at 230 and 360 nm, while XRD and SEM analysis confirmed the nanoparticles were cubic crystalline in structure with sizes ranging between 37 and 126 nm. NiO nanoparticles exhibited 79% degradation of pyrene at 2 µg/mL of anthracene within 60 min of treatment. NiO at 10 µg/mL concentration showed significant adsorption of 57%, while the adsorption method worked efficiently (72%) at 5 pH. Photocatalytic degradation was confirmed by isotherm and kinetic studies through monolayer adsorption and pseudo-first-order kinetics. Further, the absorption process was confirmed by performing GC-MS analysis of the NiO nanoparticles. On the other hand, NiO nanoparticles showed antimicrobial activity against Gram negative and Gram-positive bacteria. Therefore, the present work is one of its kind proving the dual application of NiO nanoparticles, which makes them suitable candidates for bioremediation by treating PAHs and killing pathogenic bacteria.


Subject(s)
Nickel , Polycyclic Aromatic Hydrocarbons , Nickel/chemistry , Polycyclic Aromatic Hydrocarbons/chemistry , Metal Nanoparticles/chemistry , Catalysis , Photolysis , Ultraviolet Rays , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Anthracenes/chemistry , Adsorption
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