Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 9.856
Filter
1.
Sci Rep ; 14(1): 15095, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956125

ABSTRACT

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.


Subject(s)
Elastin , Nanogels , Prostatic Neoplasms, Castration-Resistant , Male , Elastin/chemistry , Humans , Cell Line, Tumor , Nanogels/chemistry , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/metabolism , Drug Delivery Systems , Cell Survival/drug effects , Drug Liberation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Benzopyrans , Butyrates
2.
J Environ Manage ; 365: 121650, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38968881

ABSTRACT

Enhancing the coal-based fulvic acid (FA) yield through the effect of oxidation methods was of great importance. However, the realization of an efficient and environmentally friendly method for the preparation of FA, along with understanding of its formation mechanism, remains imperative. Herein, coal-based FA was prepared by oxidizing lignite with H2O2 and NaOH/KOH. The experimental data showed that ML lignite was pickled with HCl, metal ions such as iron, aluminum, and calcium can be removed, and this lignite is used as raw material, the reaction time was 150 min, the reaction temperature was 50 °C, and the volume ratio of H2O2 (30%) to KOH (3 mol/L) was 1:1, the effect of H2O2 and KOH on FA extraction was the best. The coal-based FA yield could reach 60.49%. The addition of silicone defoaming agent during the experiment resulted in a significant diminished the presence of bubbles and prevent the production of CO2. A decrease in N2 content was detected by GC. The FTIR, XPS, Py-GC/MS and other characterization results showed that FA has more polar functional groups (-COOH, -OH), and it contains more O-CO structure. Consequently, a greater quantity of FA molecules is generated during the reaction process. Moreover, the partial Gibbs free energies during the formation process of coal-based FA were calculated by density-functional theory (DFT). The highest energy required for free radicals was found to be between 1.3 and 1.7 eV. This study would provide theoretical support for exploring the FA formation process and the promotion of lignite humification by adding H2O2 or alkali to lignite.


Subject(s)
Benzopyrans , Coal , Benzopyrans/chemistry , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Spectroscopy, Fourier Transform Infrared
3.
Sci Rep ; 14(1): 16363, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013947

ABSTRACT

Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]). We converted WT genes to NS5A Q24K/L28M/R30Q/A92K or Q24/L28K/R30E/A92K. Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Compared with the WT, the Q24K/L28M/R30E/A92K RASs was 640,000-fold resistant to daclatasvir and ledipasvir, 150,000-fold resistant to velpatasvir, 44,000-fold resistant to elbasvir, and 1500-fold resistant to pibrentasvir. The Q24K/L28M/R30E/A92K RASs was 816.3 times more resistant to pibrentasvir than the Q24K/L28M/R30Q/A92K RASs. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs.


Subject(s)
Antiviral Agents , Benzimidazoles , Drug Resistance, Viral , Hepacivirus , Imidazoles , Viral Nonstructural Proteins , Hepacivirus/drug effects , Hepacivirus/genetics , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/antagonists & inhibitors , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Drug Resistance, Viral/genetics , Drug Resistance, Viral/drug effects , Benzimidazoles/pharmacology , Imidazoles/pharmacology , Carbamates/pharmacology , Fluorenes/pharmacology , Sofosbuvir/pharmacology , Pyrrolidines/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Valine/analogs & derivatives , Valine/pharmacology , Genotype , Replicon/drug effects , Replicon/genetics , Sulfonamides/pharmacology , Benzofurans/pharmacology , Pyrazines/pharmacology , Benzopyrans , RNA-Dependent RNA Polymerase
4.
Sci Rep ; 14(1): 15287, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961106

ABSTRACT

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.


Subject(s)
Benzopyrans , Cell Proliferation , Galectin 3 , Matrix Metalloproteinase 9 , Uterine Cervical Neoplasms , Humans , Matrix Metalloproteinase 9/metabolism , Benzopyrans/pharmacology , Female , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Galectin 3/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Molecular Docking Simulation , Galectins/metabolism , Galectins/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Apoptosis/drug effects , HeLa Cells , Blood Proteins
5.
PeerJ ; 12: e17642, 2024.
Article in English | MEDLINE | ID: mdl-38978754

ABSTRACT

Background: Gingivitis is an inflammation of the gums that is the initial cause of the development of periodontal disease by the activity of Nuclear Factor-kappa B (NF-κB), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), p38, and Tumor Necrosis Factor-α (TNF-α). Unaddressed chronic inflammation can lead to persistent disturbances in other parts of the body. Brazilin is a naturally occurring plant chemical that may have antibacterial and anti-inflammatory effects. Treatment based on the natural plant compound, brazilin, is developed in the form of a topical cream for easy application. Objective: The aim is to develop the natural compound brazilin in the form of a topical cream as an anti-inflammatory agent to reduce NF-κB expression through Imunohistochemistry (IHC) methods, and the expression of pro-inflammatory genes IL-1ß, IL-6, p38, and TNF-α. Methods: Male Sprague-Dawley rats were induced with gingivitis using P. gingivalis bacteria. The observed groups included rats treated with a single application of brazilin cream and rats treated with two applications of brazilin cream. The treatment was administered for 15 days. On days 3, 6, 9, 12, and 15, anatomical wound observations and wound histology using hematoxylin-eosin and Masson's Trichrome staining were performed. NF-κB protein expression was analyzed using the IHC method. Gingival inflammation gene expression of NF-κB, IL-1ß, IL-6, p38, and TNF-α was measured using q-RTPCR. Results: Single and double applications of brazilin cream increased angiogenesis and decreased NF-κB protein expression, in addition to the IL-1ß, IL-6, p38, and TNF-α gene expressions. Conclusion: In a rat gingivitis model, Brazilin cream may function as an anti-inflammatory agent in the gingival tissue.


Subject(s)
Benzopyrans , Caesalpinia , Gingivitis , NF-kappa B , Rats, Sprague-Dawley , Animals , Caesalpinia/chemistry , Male , Rats , Benzopyrans/pharmacology , Benzopyrans/administration & dosage , Benzopyrans/therapeutic use , NF-kappa B/metabolism , Gingivitis/drug therapy , Gingivitis/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Periodontal Diseases/drug therapy , Interleukin-1beta/metabolism , Interleukin-1beta/genetics , Disease Models, Animal , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Interleukin-6/metabolism , Interleukin-6/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
6.
J Agric Food Chem ; 72(28): 15801-15810, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38962874

ABSTRACT

Fungal azaphilones have attracted widespread attention due to their significant potential as sources of food pigments and pharmaceuticals. Genome mining and gene cluster activation represent powerful tools and strategies for discovering novel natural products and bioactive molecules. Here, a putative azaphilone biosynthetic gene cluster lut from the endophytic fungus Talaromyces sp. was identified through genome mining. By overexpressing the pathway-specific transcription factor LutB, five new sclerotiorin-type azaphilones (1, 6, 8, and 10-11) together with seven known analogues (2-5, 7, 9, 12) were successfully produced. Compounds 8 and 9 exhibited antibacterial activity against Bacillus subtilis with MIC values of 64 and 16 µg/mL, respectively. Compound 11 showed cytotoxic activity against HCT116 and GES-1 with IC50 values of 10.9 and 4.9 µM, respectively, while 1, 4, 5, and 7-10 showed no obvious cytotoxic activity. Gene inactivation experiments confirmed the role of the lut cluster in the production of compounds 1-12. Subsequent feeding experiments unveiled the novel functional diversity of the dual megasynthase system. Furthermore, a LutC-LutD binary oxidoreductase system was discovered, and in combination with DFT calculations, the basic biosynthetic pathway of the sclerotiorin-type azaphilones was characterized. This study provided a good example for the discovery of new azaphilones and further uncovered the biosynthesis of these compounds.


Subject(s)
Benzopyrans , Fungal Proteins , Multigene Family , Pigments, Biological , Talaromyces , Talaromyces/genetics , Talaromyces/metabolism , Talaromyces/chemistry , Pigments, Biological/chemistry , Pigments, Biological/metabolism , Humans , Benzopyrans/pharmacology , Benzopyrans/chemistry , Benzopyrans/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Endophytes/genetics , Endophytes/metabolism , Endophytes/chemistry , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Cell Line, Tumor
7.
Clin Transl Sci ; 17(7): e13884, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39004798

ABSTRACT

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.


Subject(s)
Antiviral Agents , Carbamates , Drug Administration Schedule , Drug Combinations , Hepatitis C, Chronic , Heterocyclic Compounds, 4 or More Rings , Renal Dialysis , Sofosbuvir , Humans , Sofosbuvir/pharmacokinetics , Sofosbuvir/administration & dosage , Carbamates/pharmacokinetics , Carbamates/administration & dosage , Male , Middle Aged , Female , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Hepatitis C, Chronic/drug therapy , Antiviral Agents/pharmacokinetics , Antiviral Agents/administration & dosage , Prospective Studies , Aged , Adult , Treatment Outcome , Hepacivirus/drug effects , Hepacivirus/isolation & purification , Benzimidazoles , Benzopyrans
8.
Mar Drugs ; 22(6)2024 May 26.
Article in English | MEDLINE | ID: mdl-38921552

ABSTRACT

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1-3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5-17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 µM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 µg/mL to 256 µg/mL.


Subject(s)
Anti-Bacterial Agents , Benzopyrans , Microbial Sensitivity Tests , Pigments, Biological , Zebrafish , Animals , Benzopyrans/pharmacology , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Pigments, Biological/pharmacology , Pigments, Biological/isolation & purification , Pigments, Biological/chemistry , Staphylococcus aureus/drug effects , Candida albicans/drug effects , Aquatic Organisms , Escherichia coli/drug effects , China , Cell Line
9.
Mar Drugs ; 22(6)2024 May 27.
Article in English | MEDLINE | ID: mdl-38921553

ABSTRACT

Subjecting the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (1-3), along with the known analogue coelomycin (4), as well as a new azaphilone, noonaphilone A (5). Structures were assigned to 1-5 on the basis of a detailed spectroscopic analysis, and in the case of 1-2, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for 1-4, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, 2 incorporates a rare meta-Tyr motif, typically only reported in a limited array of Streptomyces metabolites. Similarly, a plausible biosynthetic pathway is proposed for 5, highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7R noonaphilone A (5) versus the 7S deflectin 1a (6).


Subject(s)
Aspergillus , Aspergillus/metabolism , Aspergillus/chemistry , Australia , Diketopiperazines/chemistry , Diketopiperazines/isolation & purification , Aquatic Organisms , Biosynthetic Pathways , Crystallography, X-Ray , Molecular Structure , Benzopyrans , Pigments, Biological
10.
Sci Rep ; 14(1): 14270, 2024 06 20.
Article in English | MEDLINE | ID: mdl-38902414

ABSTRACT

Drought stress can have negative impacts on crop productivity. It triggers the accumulation of reactive oxygen species, which causes oxidative stress. Limited water and nutrient uptake under drought stress also decreases plant growth. Using cobalt and fulvic acid with biochar in such scenarios can effectively promote plant growth. Cobalt (Co) is a component of various enzymes and co-enzymes. It can increase the concentration of flavonoids, total phenols, antioxidant enzymes (peroxidase, catalase, and polyphenol oxidase) and proline. Fulvic acid (FA), a constituent of soil organic matter, increases the accessibility of nutrients to plants. Biochar (BC) can enhance soil moisture retention, nutrient uptake, and plant productivity during drought stress. That's why the current study explored the influence of Co, FA and BC on chili plants under drought stress. This study involved 8 treatments, i.e., control, 4 g/L fulvic acid (4FA), 20 mg/L cobalt sulfate (20CoSO4), 4FA + 20CoSO4, 0.50%MFWBC (0.50 MFWBC), 4FA + 0.50MFWBC, 20CoSO4 + 0.50MFWBC, 4FA + 20CoSO4 + 0.50MFWBC. Results showed that 4 g/L FA + 20CoSO4 with 0.50MFWBC caused an increase in chili plant height (23.29%), plant dry weight (28.85%), fruit length (20.17%), fruit girth (21.41%) and fruit yield (25.13%) compared to control. The effectiveness of 4 g/L FA + 20CoSO4 with 0.50MFWBC was also confirmed by a significant increase in total chlorophyll contents, as well as nitrogen (N), phosphorus (P), and potassium (K) in leaves over control. In conclusion4g/L, FA + 20CoSO4 with 0.50MFWBC can potentially improve the growth of chili cultivated in drought stress. It is suggested that 4 g/L FA + 20CoSO4 with 0.50MFWBC be used to alleviate drought stress in chili plants.


Subject(s)
Benzopyrans , Capsicum , Charcoal , Cobalt , Droughts , Mangifera , Capsicum/growth & development , Capsicum/metabolism , Capsicum/physiology , Cobalt/metabolism , Cobalt/analysis , Mangifera/growth & development , Mangifera/metabolism , Fruit/metabolism , Fruit/growth & development , Stress, Physiological , Soil/chemistry
11.
Sci Rep ; 14(1): 12878, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38834651

ABSTRACT

In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D­QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.


Subject(s)
Anti-Bacterial Agents , Apoptosis , Benzopyrans , Microbial Sensitivity Tests , Molecular Docking Simulation , Quantitative Structure-Activity Relationship , Sulfonamides , Sulfonamides/chemistry , Sulfonamides/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Benzopyrans/chemistry , Benzopyrans/pharmacology , Apoptosis/drug effects , Mice , Animals , Cell Line
12.
Phytochemistry ; 225: 114200, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38936530

ABSTRACT

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.


Subject(s)
Anti-Inflammatory Agents , Benzopyrans , Rhododendron , Terpenes , Rhododendron/chemistry , Terpenes/chemistry , Terpenes/pharmacology , Terpenes/isolation & purification , Mice , RAW 264.7 Cells , Animals , Benzopyrans/pharmacology , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Molecular Structure , Structure-Activity Relationship , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Nitric Oxide/biosynthesis , Nitric Oxide/antagonists & inhibitors , Dose-Response Relationship, Drug
13.
Food Chem ; 455: 139875, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38823145

ABSTRACT

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from ß-cyclodextrin (ß-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 µg mL-1 with a limit of detection at 0.027 µg mL-1 and a limit of quantification at 0.089 µg mL-1. Notably, the proposed ß-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host-guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring.


Subject(s)
Benzhydryl Compounds , Benzopyrans , Food Contamination , Food Packaging , Hydrogels , Indoles , Nitro Compounds , Phenols , beta-Cyclodextrins , Phenols/chemistry , Phenols/analysis , beta-Cyclodextrins/chemistry , Hydrogels/chemistry , Benzhydryl Compounds/chemistry , Benzhydryl Compounds/analysis , Food Packaging/instrumentation , Benzopyrans/chemistry , Indoles/chemistry , Nitro Compounds/chemistry , Food Contamination/analysis , Limit of Detection , Endocrine Disruptors/analysis , Endocrine Disruptors/chemistry
14.
ACS Nano ; 18(24): 15978-15990, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38847448

ABSTRACT

Sulfur-substituted dicyanomethylene-4H-chromene (DCM) derivatives based on the intramolecular charge transfer (ICT) mechanism were designed as near-infrared (NIR) fluorescent dyes. Using the Knoevenagel condensation method, the S-DCM-OH(835) fluorescence dye was synthesized, which had an emission wavelength exceeding 800 nm and 220 nm of a Stokes shift. Compared to commercial ICG, S-DCM-OH(835) was not only synchronized in emission wavelength but also far superior in Stokes shifts. These advantages made the design of S-DCM-NIR(835) based on this dye potentially valuable for biological applications. Based on this chemical structure, a fluorescent S-DCM-NIR(835) nanoprobe with a mean diameter of 17.69 nm was fabricated as the NIR imaging nanoprobe. Results showed that the nanoprobe maintained the high-specificity identification of cysteine (Cys) via the Michael addition reaction, with the detection limitation of 0.11 µM endogenous Cys. More importantly, in an ischemic stroke mouse model, the S-DCM-NIR(835) nanoprobe could monitor the Cys concentration change at stroke lesion due to the disruption of Cys metabolism under the ischemic stroke condition. Such a S-DCM-NIR(835) nanoprobe could not only differentiate the severity of the ischemic stroke using response time but also quantify the concentration of Cys in real-time in vivo.


Subject(s)
Cysteine , Fluorescent Dyes , Infrared Rays , Ischemic Stroke , Fluorescent Dyes/chemistry , Animals , Cysteine/chemistry , Mice , Ischemic Stroke/diagnostic imaging , Optical Imaging , Nanoparticles/chemistry , Humans , Spectroscopy, Near-Infrared/methods , Male , Benzopyrans/chemistry
15.
Sci Rep ; 14(1): 13506, 2024 06 12.
Article in English | MEDLINE | ID: mdl-38866882

ABSTRACT

Xenocoumacin 1 (Xcn 1), antibiotic discovered from secondary metabolites of Xenorhabdus nematophila, had the potential to develop into a new pesticide due to its excellent activity against bacteria, oomycetes and fungi. However, the current low yield of Xcn1 limits its development and utilization. To improve the yield of Xcn1, response surface methodology was used to determine the optimal composition of fermentation medium and one factor at a time approach was utilized to optimize the fermentation process. The optimal medium composed of in g/L: proteose peptone 20.8; maltose 12.74; K2HPO4 3.77. The optimal fermentation conditions were that 25 °C, initial pH 7.0, inoculum size 10%, culture medium 75 mL in a 250 mL shake flask with an agitation rate of 150 rpm for 48 h. Xenorhabdus nematophila YL001 was produced the highest Xcn1 yield (173.99 mg/L) when arginine was added to the broth with 3 mmol/L at the 12th h. Compared with Tryptic Soy Broth medium, the optimized fermentation process resulted in a 243.38% increase in Xcn1 production. The obtained results confirmed that optimizing fermentation technology led to an increase in Xcn1 yield. This work would be helpful for efficient Xcn1 production and lay a foundation for its industrial production.


Subject(s)
Culture Media , Fermentation , Xenorhabdus , Xenorhabdus/metabolism , Culture Media/chemistry , Hydrogen-Ion Concentration , Anti-Bacterial Agents/biosynthesis , Benzopyrans
16.
Anal Chem ; 96(26): 10860-10869, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38889184

ABSTRACT

Single-molecule localization microscopy (SMLM) requires high-intensity laser irradiation, typically exceeding kW/cm2, to yield a sufficient photon count. However, this intense visible light exposure incurs substantial cellular toxicity, hindering its use in living cells. Here, we developed a class of near-infrared (NIR) spontaneously blinking fluorophores for SMLM. These NIR fluorophores are a combination of rhodamine spirolactams and merocyanine derivatives, where the rhodamine spirolactam component converts between a bright and dark state based on pH-dependent spirocyclization and merocyanine derivatives shift the excitation wavelength into the infrared. Single-molecule characterizations demonstrated their potential for SMLM. At a moderate power density of 3.93 kW/cm2, these probes exhibit duty cycle as low as 0.18% and an emission rate as high as 26,700 photons/s. Phototoxicity assessment under single-molecule imaging conditions reveals that NIR illumination (721 nm) minimizes harm to living cells. Employing these NIR fluorophores, we successfully captured time-lapse super-resolution tracking of mitochondria at a Fourier ring correlation (FRC) resolution of 69.4 nm and reconstructed the ultrastructures of endoplasmic reticulum (ER) in living cells.


Subject(s)
Fluorescent Dyes , Infrared Rays , Fluorescent Dyes/chemistry , Humans , HeLa Cells , Indoles/chemistry , Rhodamines/chemistry , Microscopy, Fluorescence , Cell Survival/drug effects , Mitochondria , Benzopyrans
17.
PeerJ ; 12: e17360, 2024.
Article in English | MEDLINE | ID: mdl-38737746

ABSTRACT

Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future.


Subject(s)
Benzopyrans , Breast Neoplasms , Cadherins , Epithelial-Mesenchymal Transition , Female , Humans , Benzopyrans/pharmacology , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Cadherins/metabolism , Cell Line, Tumor , Epithelial-Mesenchymal Transition/drug effects , Matrix Metalloproteinases/metabolism , Matrix Metalloproteinases/genetics , MCF-7 Cells , Neoplasm Invasiveness/genetics , Nuclear Proteins , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/genetics , Twist-Related Protein 1/metabolism , Twist-Related Protein 1/genetics , Vimentin/metabolism , Vimentin/genetics
18.
J Hazard Mater ; 473: 134595, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38761769

ABSTRACT

A biocatalytic system comprising fungal laccase and mediators can generate phenol radicals and efficiently eliminate various triarylmethane dyes. This study systematically explores the kinetic impact of dissolved organic matter (DOM), represented by humic substance (HS consisting of 90% fulvic acid, from lignite), on the decolorization of seven typical triarylmethane dyes by Trametes versicolor laccase and twenty natural mediators. Among these, 4-hydroxybenzyl alcohol (4-HA) and methyl violet (MV) undergo in-depth investigation regarding degradation products, pathways, and reaction mechanisms. In instances where HS hampers laccase-alone decolorization, such as malachite green, Coomassie brilliant blue, bromophenol blue, and acid magenta, this inhibition may persist despite mediator introduction. Conversely, in cases where HS facilitates decolorization, such as crystalline violet and ethyl violet, most laccase-mediator systems (LMSs) can still benefit. For MV decolorization by laccase and 4-HA, HS's kinetic effect is controlled by concentration and reaction time. A 5 mg/L HS increased the decolorization rate from 50% to 67% within the first hour, whereas 10 mg/L HS only achieved 45%. After 16 h of reaction, HS's impact on decolorization rate diminishes. Furthermore, the addition of HS enhances precipitation production, probably due to its involvement in polymerization with MV and mediator. Computational simulations and spectral monitoring reveal that low HS concentrations accelerate laccase-mediated demethylation by disrupting the chromophores bound to MV, thus promoting the decolorization of MV. Conversely, inhibition by high HS concentrations stems from the competitive binding of the enzyme pocket to the mediator, and the reduction of phenol free radicals in the system. Molecular docking and kinetic simulations revealed that laccase forms complexes with both the mediator and MV. Interestingly, the decolorization of MV occurred through a non-radical mechanism in the presence of HS. This work provided a reference for screening of high catalytic performance mediators to remove triarylmethane dyes in the actual water environment.


Subject(s)
Coloring Agents , Laccase , Laccase/metabolism , Laccase/chemistry , Coloring Agents/chemistry , Humic Substances , Kinetics , Water Pollutants, Chemical/chemistry , Benzopyrans/chemistry , Molecular Docking Simulation , Polyporaceae/enzymology
19.
Carbohydr Res ; 541: 109164, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38815342

ABSTRACT

Stereoselective synthesis is essential for propelling mainstream academia toward a relentless pursuit of novel and cutting-edge strategies for constructing molecules with unparalleled precision. Naturally derived benzopyrans, benzopyrones, and flavonoids are an essentially prominent group of oxa-heterocycles, highly significant targets in medicinal chemistry owing to their extensive abundance in biologically active natural products and pharmaceuticals. The molecular complexity and stereoselectivity induced by heterocycles embedded with C-glycosides have attracted considerable interest and emerged as a fascinating area of research for synthetic organic chemists. This present article emphasizes the existing growths in the strategies involving the diastereoselective synthesis of C-glycosylated benzopyrans, benzopyrones, and flavonoids using naturally acquired glycones as chiral synthons.


Subject(s)
Benzopyrans , Biological Products , Flavonoids , Glycosides , Flavonoids/chemistry , Flavonoids/chemical synthesis , Stereoisomerism , Benzopyrans/chemistry , Benzopyrans/chemical synthesis , Biological Products/chemical synthesis , Biological Products/chemistry , Glycosides/chemistry , Glycosides/chemical synthesis , Pyrones/chemistry , Pyrones/chemical synthesis , Glycosylation , Molecular Structure
20.
Bioresour Technol ; 403: 130857, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763203

ABSTRACT

Immobilization technology is a promising way to improve effectiveness and stability of microbial remediation for polycyclic aromatic hydrocarbons (PAHs), in which carrier material is one of key factors restricting removal efficiency. In this study, fulvic acid-wheat straw biochar (FA/WS) composites were applied for immobilization of an efficient PAHs degrading bacterium Stenotrophomonas maltophilia (SPM). FA/WS&SPM showed superior degradation capacity than free bacteria and biochar-immobilized bacteria, with the removal efficiency of pyrene (20 mg L-1) reaching 90.5 % (7 days). Transcriptome analysis revealed that FA in the carrier materials can promote transportation and degradation of pyrene, and cell growth, as well as inhibit cell apoptosis. Enzyme activity and degradation products detection showed that SPM utilized both phthalic acid and salicylic acid metabolic pathways to degrade pyrene. Practicality of FA/WS&SPM for different kinds of PAHs remediation had been verified in contaminated soil, demonstrating a great potential in the field of PAHs polluted sites remediation.


Subject(s)
Benzopyrans , Biodegradation, Environmental , Cells, Immobilized , Pyrenes , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/metabolism , Pyrenes/metabolism , Benzopyrans/metabolism , Cells, Immobilized/metabolism , Charcoal/chemistry , Charcoal/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL