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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120313, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34474223

RESUMO

Copper ion (Cu2+) is an essential part of the living organisms. Cu2+ ions play a vital role in many biotic processes. An abnormal amount of Cu2+ ions may result in serious diseases. Herein, a novel "fluorescent ON" probe NC-Cu to trace minute levels of Cu2+ ions in presence of various biological active species has been developed. Lysosomal cells targeting group (Morpholine) was added to the probe. The spectral properties of probe NC-Cu were recorded in HEPES buffer (0.01 M, pH = 7.4, comprising 50% CH3CN, λex = 430 nm, slit: 5 nm). The synthesized probe NC-Cu work based on copper promoted catalytic hydrolysis of hydrazone and shows remarkable fluorescence enhancement. The reaction of the probe with Cu2+ ions was completed within 20 min. An excellent linear relationship (R2 = 0.9952) was found and the limit of detection (LOD, according to the 3σ/slope) for Cu2+ ions was calculated to be 5.8 µM. Furthermore, NC-Cu was effectively functional in the living cells (KYSE30 cells) to trace Cu2+ ions.


Assuntos
Cumarínicos , Corantes Fluorescentes , Cobre , Íons , Espectrometria de Fluorescência
2.
Food Chem ; 368: 130838, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34425336

RESUMO

Herein, using Fe3O4 nanoparticles (Fe3O4 NPs) as a magnetic artificial peroxidase, an "on-off" ratiometric photoluminescence sensor with high-sensitivity and high-selectivity for coumarin was constructed based on photoinduced electron transfer (PET) between 7-hydroxycoumarin and rhodamine B (RB). The results showed that Fe3O4 NPs catalyzed H2O2 to generate nucleophilic group ·OH, which attacked the active site of coumarin and produced strong fluorescent 7-hydroxycoumarin molecules. Then, the fluorescence of RB was quenched with 7-hydroxycoumarin through the PET effect. The ratio signal generated in the above process was used for the quantitative detection of coumarin. Under optimized conditions, the linear range 0.5-25 mg/L was acquired for coumarin with the detection limit of 0.016 mg/L. This method had excellent selectivity and the recovery rate was 81.8%-106.8% with the relative standard deviation less than 5.6%, so it can be used for the quantitative analysis of coumarin in complex matrix samples.


Assuntos
Peróxido de Hidrogênio , Nanopartículas , Cumarínicos , Fluorescência , Tomografia por Emissão de Pósitrons
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120408, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34592481

RESUMO

The non-covalent interactions between graphene and aromatic fluorophores have generated highly sensitive fluorimetric turn-on sensors for various significant analytes. Herein, the supramolecular interaction between reduced graphene oxide and 7-Hydroxy-4-Methyl-8-Amino Coumarin is made use of for tracing Cu2+ at sub-zeptomole level with excellent selectivity among a collection of nineteen metal ions. The system enables quantification of the analyte in a commendably wide range, from micromolar to zeptomolar, a feature that almost all-optical sensors lack. Handy solid-state sensor strip fabricated using the above-mentioned supramolecular combination enabled visual recognition of Cu2+ions at the molecular level. Based on the chemo recognition ability of the fluorophore, multiple Boolean logic devices operating at the molecular level are proposed. By screening pertinent coumarin derivatives, it is demonstrated that the selectivity and sensitivity of the sensors of this sort are decided by the number of π- interaction centers of the fluorophores and the strength by which they interact with graphene, respectively, which will enable identification and modification of proper fluorophores for ultra-trace detection of contaminants of environmental relevance from aqueous solutions.


Assuntos
Grafite , Cumarínicos , Corantes Fluorescentes , Íons , Metais
4.
Appl Microbiol Biotechnol ; 105(23): 8647-8661, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34750645

RESUMO

Quorum sensing mediated biofilm formation has a major role in modern therapeutics due to adherence of cells on the solid surface. Here, we have developed a stable polyurethane blend with a 6-methylcoumarin (6-MC) composite that showed significant antibiofilm activity. The 6-MC was found to prominently inhibit P. aeruginosa PAO1 biofilm formation at 125 µg/ml and was able to inhibit various virulence factors such as pyocyanin, siderophore, exopolysaccharide, elastase and proteases, including motility of the bacteria. In addition, 6-MC was found functionally active in saving the C. elegans from P. aeruginosa PAO1 infection. Moreover, docking studies of different activator proteins correlate well with in vitro and in vivo results. To enhance this biological activity, 6-MC was blended with polyurethane, which also revealed superior antibiofilm activity on plastic and glass surfaces compared to a polyurethane coating. Therefore, the 6-MC could be used to combat P. aeruginosa infection for effective treatment and antibiofilm applications on solid surfaces through polyurethane blending and subsequent film fabrication strategies. KEY POINTS: • 6-Methylcoumarin significantly inhibits P. aeruginosa PAO1 biofilm • 6-MC was found functionally active in saving the C. elegans from PAO1 infection • 6-MC and polyurethane blend showed superior antibiofilm activity.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Animais , Antibacterianos/farmacologia , Biofilmes , Caenorhabditis elegans , Cumarínicos , Poliuretanos , Fatores de Virulência
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 973-980, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809736

RESUMO

Objective To investigate the effect and mechanism of urolithin A (UA) on the inflammation and lipid accumulation induced by hyperlipidemia in L02 hepatocytes. Methods Nuclear erythroid 2-related factor 2 (Nrf2) short hairpin RNA (shRNA) lentivirus was used to establish a stable Nrf2 knockdown cell line in L02 cells. Empty vector control cells and Nrf2 knockdown cells were treated with free fatty acids (FFAs) or bovine serum albumin (BSA) to establish the hyperlipidemic cell model, and Urolithin A was treated on this basis. Specifically, they were divided into control group (BSA treatment), FFA treatment group (0.6 mmol/L), FFA (0.6 mmol/L) combined with UA low-dose group (10 µmol/L) and FFA (0.6 mmol/L) combined with UA high-dose group (20 µmol/L). All of these groups were treated for 48 h. The dye of BODIPY493/503 was used to detect the accumulation of lipid droplets in the cell. The levels of triglyceride (TG) was detected by TG assay kit. TNF-α and IL-6 in the supernatant of the cells were detected by ELISA. The level of cellular reactive oxygen species (ROS) was detected by flow cytometry combined with DCFH-DA. Malondialdehyde (MDA) kit was used to test the level of MDA. Total superoxide dismutase (SOD) kit and catalase (CAT) kit were used to detect the activities of total SOD and CAT, respectively. The mRNA levels of SOD2 and CAT were detected by real-time quantitative PCR. The protein levels of SOD2, CAT, Nrf2 as well as P62, LC3 were detected by Western blot analysis. The adenovirus of RFP-GFP-LC3 was used to measure the autophagy flux in the cells. Results FFA increased the levels of TNF-α, IL-6 and TG as well as the positive rate of BODIPY493/503 staining in L02 cells. The levels of MDA and ROS increased, while the mRNA and protein expressions of SOD2, CAT and Nrf2 decreased when treated with FFA. FFA treatment also suppressed the levels of autophagy markers LC33-II and promoted the level of P62, and blocked autophagy flux. UA treatment could reverse the above effects of FFA, with significant difference. When Nrf2 was knocked down, the above effects of UA disappeared. Conclusion Through activating autophagy and antioxidative pathways which are mediated by Nrf2 pathway, urolithin A alleviates inflammation and oxidative stress induced by high lipid in L02 hepatocytes.


Assuntos
Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Autofagia , Cumarínicos , Hepatócitos/metabolismo , Humanos , Inflamação , Lipídeos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio
6.
J Asian Nat Prod Res ; 23(11): 1043-1050, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34709085

RESUMO

Two new prenylated coumarins, 3'-hydroxytoddanone (1), and isotoddalolactone (2), along with four known analogues (3-6) were isolated from the roots of Zanthoxylum nitidum. Their chemical structures were elucidated based on extensive spectroscopic interpretation and HR-ESI-MS analysis. The absolute configuration of compound 2 was determined by comparing experimental ECD spectrum with that calculated by the time-dependent density functional theory (TDDFT) method. Compounds 4-6 were isolated from the Zanthoxylum genus for the first time. The two new compounds were tested for antiproliferative activities in vitro on the HL-60, K562 and THP-1 cell lines. Compounds 1 and 2 exhibited moderate cell growth inhibitory activities in vitro against human leukemic HL-60 cell lines, with IC50 values of 32.64 and 33.15 µM, respectively.


Assuntos
Zanthoxylum , Cumarínicos/farmacologia , Estrutura Molecular , Raízes de Plantas
7.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641527

RESUMO

Toddalia asiatica (L.) Lam. (Rutaceae) has shown a broad spectrum of biological properties, such as anti-inflammatory, antioxidant, antimicrobial, anti-HIV, and anticancer properties. The present study is concerned with the separation of the main components with broad partition coefficients (KD values) from T. asiatica, using linear gradient high-speed counter-current chromatography (LGCCC) combined with an off-line two-dimensional (2D) mode. Similar to the binary gradient HPLC, the LGCCC mode is operated by the adjustment of the proportion between the mobile phase of 5:5:1:9 (v/v) (pump A) and 5:5:4.5:5.5 (v/v) (pump B) in an n-hexane/ethyl acetate/methanol/water solvent system. The off-line 2D-CCC mode was used in this study for the secondary separation of two similar KD value compounds with n-hexane/ethyl acetate/methanol/water (5:5:4:6, v/v). Notably, six coumarins, namely, tomentin (1), toddalolactone (2), 5,7,8-trimethoxycoumarin (3), mexoticin (4), isopimpinellin (5), and toddanone (6), were efficiently separated. The structures of the pure compounds were elucidated by spectral techniques and compared with the literature.


Assuntos
Cumarínicos/isolamento & purificação , Distribuição Contracorrente/métodos , Raízes de Plantas/química , Rutaceae/química , Cromatografia Líquida de Alta Pressão , Cumarínicos/química , Furocumarinas/isolamento & purificação , Estrutura Molecular , Solventes/química
8.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641543

RESUMO

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a-4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 µM). In the DCF-DA assay, the 4'-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3'-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 µM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 µΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60-97%) values.


Assuntos
Cumarínicos/síntese química , Cumarínicos/farmacocinética , Inibidores de Lipoxigenase/farmacologia , Células A549 , Antioxidantes/química , Antioxidantes/farmacologia , Biomimética , Proteínas Sanguíneas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Fluoresceínas/química , Corantes Fluorescentes/química , Sequestradores de Radicais Livres/química , Humanos , Queratinócitos/efeitos dos fármacos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacocinética , Simulação de Acoplamento Molecular , Soja/enzimologia
9.
Molecules ; 26(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684900

RESUMO

Coumarins are widely distributed in nature and can be found in a large number of naturally occurring and synthetic bioactive molecules [...].


Assuntos
Cumarínicos/química , Humanos
10.
Anal Chem ; 93(42): 14256-14262, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34651497

RESUMO

A cross-reactive sensor array is powerful for high-throughput discrimination of various kinds of metal ions. However, the construction of a multicomponent sensor array is always time-consuming and cost-ineffective. Herein, a practical four-component X1-based sensor array (X1SA) was obtained by simply dissolving a single dye molecule X1 in respective solvents such as methanol, ethanol, dimethyl sulfoxide, and acetonitrile. In this design, X1 exhibits strong solvatochromic fluorescence properties via an excited-state intramolecular proton transfer and intramolecular charge transfer combined mechanism. Moreover, rotation of the C-N bond between the pyridine and coumarin units in X1 enabled it to coordinate with metal ions through different binding modes, which acted as an additional dimension of the sensor array. Inspired by this C-N bond rotation strategy, X1SA was determined to be powerful in discriminating 20 kinds of metal ions in both phosphate-buffered saline and 5% serum media in a range of 0.1-100 µM. In addition, the sensor array was also successfully applied in differentiating similar and mixed metal ions such as Fe3+/Fe2+, Cd2+/Hg2+, and Sn2+/Pb2+ in serum samples, which is meaningful for investigating the biological roles of iron and early diagnosis of related metal poisoning accidents.


Assuntos
Cumarínicos , Metais , Fluorescência , Íons , Piridinas
11.
J Agric Food Chem ; 69(44): 13055-13065, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34694785

RESUMO

This is the first study to report the distribution of urolithin metabotypes (UMs) in Asian people, specifically in the Chinese. As was reported for Europeans and Latin Americans, three UMs were observed, UM-A (54.3%), UM-B (31.4%), and UM-0 (14.3%), in 35 healthy Chinese youth. The richness and diversity of gut microbiota were lower in UM-0 than in UM-A and UM-B at the genus level. Gordonibacter in UM-A and UM-B was significantly higher than that in UM-0. The Akkermansia was not found in UM-0. The correlation analysis between the type and content of urolithins and the gut microbiota at the genus level showed that 27 genera were significantly positively correlated with urolithin A and 20 genera were significantly positively associated with isourolithin A and urolithin B. In addition, different KEGG pathways such as TCA cycle, energy metabolism, and some disease were found between the gut microbiome of the three UMs. Further research is needed to explore the mechanisms of metabotypes and the differential health benefits or illness predisposition of the three UMs.


Assuntos
Microbioma Gastrointestinal , Adolescente , China , Cumarínicos , Nível de Saúde , Humanos , Taninos Hidrolisáveis/metabolismo , Redes e Vias Metabólicas
12.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639166

RESUMO

Coumarins, natural products abundant in Melilotus albus, confer features in response to abiotic stresses, and are mainly present as glycoconjugates. UGTs (UDP-glycosyltransferases) are responsible for glycosylation modification of coumarins. However, information regarding the relationship between coumarin biosynthesis and stress-responsive UGTs remains limited. Here, a total of 189 MaUGT genes were identified from the M. albus genome, which were distributed differentially among its eight chromosomes. According to the phylogenetic relationship, MaUGTs can be classified into 13 major groups. Sixteen MaUGT genes were differentially expressed between genotypes of Ma46 (low coumarin content) and Ma49 (high coumarin content), suggesting that these genes are likely involved in coumarin biosynthesis. About 73.55% and 66.67% of the MaUGT genes were differentially expressed under ABA or abiotic stress in the shoots and roots, respectively. Furthermore, the functions of MaUGT68 and MaUGT186, which were upregulated under stress and potentially involved in coumarin glycosylation, were characterized by heterologous expression in yeast and Escherichia coli. These results extend our knowledge of the UGT gene family along with MaUGT gene functions, and provide valuable findings for future studies on developmental regulation and comprehensive data on UGT genes in M. albus.


Assuntos
Cumarínicos/metabolismo , Genoma de Planta , Glucuronosiltransferase/metabolismo , Melilotus/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Difosfato de Uridina/metabolismo , Cromossomos de Plantas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Glucuronosiltransferase/genética , Glicosilação , Melilotus/genética , Melilotus/crescimento & desenvolvimento , Filogenia , Proteínas de Plantas/genética , Transcriptoma
13.
J Phys Chem B ; 125(41): 11557-11565, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34633826

RESUMO

A judicious strategy was utilized to envision the substantial regio-positional effects of substituents on the photophysical properties of the 2H-chromen-2-one-3-benzothiazole scaffold-based push-pull framework, named 6-X-CUMs. Among them, 6-NEt2-CUM reveals prominent excited-state intramolecular charge transfer with a large change of dipole moment (Δµ ∼ 18.23 D), hence displaying remarkable emission solvatochromism from the green (536 nm in cyclohexane) to far-red region (714 nm in dimethyl sulfoxide) and a high-temperature sensitivity (-0.23 nm °C-1). These, together with unique basicity and acido-/vaporchromism upon acidification elucidated by NMR and photospectroscopic studies, show stark contrast to the conventional 7-NEt2-CUM. The new series of these tailored 6-X-CUMs represents a new dimension in tailoring the photophysical properties for the development of a promising class of multistimuli-responsive materials.


Assuntos
Cumarínicos , Solventes
14.
J Chem Inf Model ; 61(10): 5028-5053, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34648283

RESUMO

The estrogen receptor α (ERα) represents a 17ß-estradiol-inducible transcriptional regulator that initiates the RNA polymerase II-dependent transcriptional machinery, pointed for breast cancer (BC) development via either genomic direct or genomic indirect (i.e., tethered) pathway. To develop innovative ligands, structure-based (SB) three-dimensional (3-D) quantitative structure-activity relationship (QSAR) studies have been undertaken from structural data taken from partial agonists, mixed agonists/antagonists (selective estrogen receptor modulators (SERMs)), and full antagonists (selective ERα downregulators (SERDs)) correlated with either wild-type or mutated ERα receptors. SB and ligand-based (LB) alignments allow us to rule out guidelines for the SB/LB alignment of untested compounds. 3-D QSAR models for ERα ligands, coupled with SB/LB alignment, were revealed to be useful tools to dissect the chemical determinants for ERα-based anticancer activity as well as to predict their potency. The herein developed protocol procedure was verified through the design and potency prediction of 12 new coumarin-based SERMs, namely, 3DQ-1a to 3DQ-1e, that upon synthesis turned to be potent ERα antagonists by means of either in vitro or in vivo assays (described in the second part of this study).


Assuntos
Neoplasias da Mama , Receptor alfa de Estrogênio , Neoplasias da Mama/tratamento farmacológico , Cumarínicos , Estradiol , Moduladores de Receptor Estrogênico , Feminino , Humanos , Ligantes , Relação Quantitativa Estrutura-Atividade
15.
Phytomedicine ; 93: 153741, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34656886

RESUMO

BACKGROUND: Pancreatic inflammation plays a key role in diabetes pathogenesis and progression. Urolithin A (UA), an intestinal flora metabolite of pomegranate, has anti-diabetic, anti-inflammatory and kidney protection effects among others. However, its effects on pancreatic inflammation and the potential mechanisms have not been clearly established. PURPOSE: This study aimed at investigating the molecular mechanisms of UA anti-pancreatic inflammation under a diabetic environment. METHODS: Diabetes induction in male C57BL/6 mice was achieved by a high fat diet and intraperitoneal streptozotocin injections. Then, diabetic mice were orally administered with UA for 8 weeks. In vitro, endoplasmic reticulum stress and MIN6 pancreatic ß cell inflammation were induced using 25 mM glucose and 0.5 mM palmitic acid. The effects of UA were evaluated by immunohistochemistry, Western blot, and enzyme linked immunosorbent assays. Finally, the underlying mechanisms were elucidated using an autophagy inhibitor (chloroquine, CQ) and an AMPK inhibitor (dorsomorphin dihydrochloride). RESULTS: UA significantly inhibited IL-1ß secretion and TXNIP/NLRP3 expression in the pancreas of diabetic mice and in MIN6 pancreatic cells. UA downregulated the ER stress protein, p-PERK, and promoted AMPK phosphorylation. UA activated autophagy to inhibit TXNIP/NLRP3 IL-1ß inflammatory signal, an effect that was reversed by CQ. Dorsomorphin 2HCL, reversed the autophagy-activation and anti-inflammatory effects of UA. Verapamil, clinically applied as an antiarrhythmic drug, is a TXNIP inhibitor for prevention of beta cell loss and diabetes development, but limited by its cardiac toxicity. In this study, verapamil (as positive control) inhibited NLRP3 /IL-1ß signaling in MIN6 cells. Inhibitory effects of UA on TXNIP and IL-1ß were weaker than those of verapamil (both at 50 µM, p < 0.05, p < 0.01). Conversely, inhibitory effects of UA on p62 were stronger, relative to those of verapamil (p < 0.05), and there were no differences in AMPK activation and LC3 enhancement effects between UA and verapamil. CONCLUSION: UA is a potential anti-pancreatic inflammation agent that activates AMPK and autophagy to inhibit endoplasmic reticulum stress associated TXNIP/NLRP3/IL-1ß signal pathway.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Proteínas de Transporte , Cumarínicos , Diabetes Mellitus Experimental/tratamento farmacológico , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Tiorredoxinas/metabolismo
16.
Molecules ; 26(20)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684845

RESUMO

4-Hydroxycoumarin (4HC) has been used as a lead compound for the chemical synthesis of various bioactive substances and drugs. Its prenylated derivatives exhibit potent antibacterial, antitubercular, anticoagulant, and anti-cancer activities. In doing this, E. coli BL21(DE3)pLysS strain was engineered as the in vivo prenylation system to produce the farnesyl derivatives of 4HC by coexpressing the genes encoding Aspergillus terreus aromatic prenyltransferase (AtaPT) and truncated 1-deoxy-D-xylose 5-phosphate synthase of Croton stellatopilosus (CstDXS), where 4HC was the fed precursor. Based on the high-resolution LC-ESI(±)-QTOF-MS/MS with the use of in silico tools (e.g., MetFrag, SIRIUS (version 4.8.2), CSI:FingerID, and CANOPUS), the first major prenylated product (named compound-1) was detected and ultimately elucidated as ferulenol, in which information concerning the correct molecular formula, chemical structure, substructures, and classifications were obtained. The prenylated product (named compound-2) was also detected as the minor product, where this structure proposed to be the isomeric structure of ferulenol formed via the tautomerization. Note that both products were secreted into the culture medium of the recombinant E. coli and could be produced without the external supply of prenyl precursors. The results suggested the potential use of this engineered pathway for synthesizing the farnesylated-4HC derivatives, especially ferulenol.


Assuntos
Cumarínicos/metabolismo , Escherichia coli/metabolismo , 4-Hidroxicumarinas/metabolismo , Aspergillus/metabolismo , Simulação por Computador , Dimetilaliltranstransferase/metabolismo , Cinética , Prenilação/fisiologia
17.
J Chromatogr A ; 1657: 462586, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34689906

RESUMO

Coumarin is a phytotoxin found in the popular spice cinnamon, which is used to flavor many Asian curry dishes. In this work, we developed and compared the analytical performance of reversed-phase liquid chromatography (RP-LC) and sweeping-micellar electrokinetic chromatography (MEKC) methods for the determination of coumarin in complex curry (gravy) samples. Using a matrix matched sample (curry after solvent extraction with methanol and diluted with 100 mM phosphoric acid), the intra-day and inter-day repeatability of retention/migration time and (corrected) peak area for both methods were acceptable (%RSD (n=6) ≤ 5%). The linear range and limit of quantitation (LOQ) were an order of magnitude better in RP-LC (RP-LC linear range = 0.11-108 mg/kg, LOQ = 0.11 mg/kg) (Sweeping-MEKC linear range = 2.16-216 mg/kg, LOQ = 2.16 mg/kg). However, the limit of detection (S/N=3) and LOQ in sweeping-MEKC was 0.65 mg/kg and 2.16 mg/kg, which were sufficient to report the levels of coumarin ≥ the European limit of 2 mg/kg in foods. During the analysis of 25 curry samples, relatively similar results for sweeping-MEKC and RP-LC were obtained for 6 samples that contained coumarin >LOQ of sweeping-MEKC. Interferences in RP-LC lead to significant overestimation of coumarin levels in 3 samples. Coumarin levels above the EU limit was found in 6 curry samples using the more selective sweeping-MEKC. This work should also raise public awareness on the presence of potentially high levels of coumarin in some foods.


Assuntos
Cromatografia Capilar Eletrocinética Micelar , Cromatografia de Fase Reversa , Cumarínicos , Metanol , Micelas
18.
Eur J Pharm Sci ; 167: 106022, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34592461

RESUMO

The effect of some deep eutectic solvents (DESs) on the coumarin solubility has been investigated using Hansen solubility parameters (HSP). The solubility of coumarin was measured in aqueous systems containing some DESs based on choline chloride (ChCl) as hydrogen bond acceptor (HBA) with urea (U), ethylene glycol (EG), and glycerol (GLY) as hydrogen bond donors (HBD) by widely applied shake-flask method at T = (298.15 to 313.15) K. The results indicate that coumarin solubility enhances with the concentration of DESs and temperature. Also, coumarin was dissolved more than 80 times compared with pure water in the presence of ChCl/EG. Then experimental data were fitted to Wilson, electrolyte Non-Random Tow-Liquid (e-NRTL), and UNIQUAC activity coefficient models. Furthermore, the dissolution thermodynamic properties including enthalpy, Gibbs free energy, and entropy have been calculated based on Gibbs and van't Hoff equations. Due to these results, it is indicated that coumarin dissolution in the studied systems is an endothermic process. Moreover, to investigate the biological properties of DESs, MTT assay have been applied to determinate cytotoxicity of the DESs. In the melanoma skin cell line, cell culture tests revealed that these solvents had very low toxicity and high biocompatibility.


Assuntos
Colina , Preparações Farmacêuticas , Cumarínicos/toxicidade , Solubilidade , Solventes
19.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500576

RESUMO

Steroid hormones play an essential role in a wide variety of actions in the body, such as in metabolism, inflammation, initiating and maintaining sexual differentiation and reproduction, immune functions, and stress response. Androgen, aromatase, and sulfatase pathway enzymes and nuclear receptors are responsible for steroid biosynthesis and sensing steroid hormones. Changes in steroid homeostasis are associated with many endocrine diseases. Thus, the discovery and development of novel drug candidates require a detailed understanding of the small molecule structure-activity relationship with enzymes and receptors participating in steroid hormone synthesis, signaling, and metabolism. Here, we show that simple coumarin derivatives can be employed to build cost-efficiently a set of molecules that derive essential features that enable easy discovery of selective and high-affinity molecules to target proteins. In addition, these compounds are also potent tool molecules to study the metabolism of any small molecule.


Assuntos
Proteínas de Transporte/metabolismo , Cumarínicos/farmacologia , Esteroides/metabolismo , Animais , Humanos , Ligação Proteica/fisiologia , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
20.
Molecules ; 26(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500814

RESUMO

The investigation of the constituents of the rhizomes of Dioscorea collettii afforded one new dihydroisocoumarin, named (-)-montroumarin (1a), along with five known compounds-montroumarin (1b), 1,1'-oxybis(2,4-di-tert-butylbenzene) (2), (3R)-3'-O-methylviolanone (3a), (3S)-3'-O-methylviolanone (3b), and (RS)-sativanone (4). Their structures were elucidated using extensive spectroscopic methods. To the best of our knowledge, compound 1a is a new enantiomer of compound 1b. The NMR data of compound 2 had been reported but its structure was erroneous. The structure of compound 2 was revised on the basis of a reinterpretation of its NMR data (1D and 2D) and the assignment of the 1H and 13C NMR data was given rightly for the first time. Compounds 3a-4, three dihydroisoflavones, were reported from the Dioscoreaceae family for the first time. The cytotoxic activities of all the compounds were tested against the NCI-H460 cell line. Two dihydroisocoumarins, compounds 1a and 1b, displayed moderate cytotoxic activities, while the other compounds showed no cytotoxicity.


Assuntos
Cumarínicos/química , Dioscorea/química , Isoflavonas/química , Rizoma/química , Derivados de Benzeno/química , Linhagem Celular Tumoral , Cumarínicos/toxicidade , Humanos , Isoflavonas/toxicidade , Extratos Vegetais/química
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