JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2020
·
IF 4.673
L. Ravithej Singh,Yu-Lin Chen,Yuan-Yuan Xie,Wei Xia,Xing-Wen Gong,Robert C. Hider,Tao Zhou
In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 μM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 μM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.
研究领域:
药物化学
·
生物化学
✓ 已验证
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Zhanming Tang,Yanyan Miao,Huimin Lu,Chao Chen,Shiming Li,Wensheng Zhang
Citri Reticulatae Pericarpium (Xinhui Chenpi) , a representative product with a protected geographical indication from Xinhui District, Guangdong Province, China, is a dual-use medicinal and edible material and a traditional medicinal resource whose quality is traditionally believed to improve with prolonged aging. Increasing evidence indicates that the succession of surface microbial communities and their metabolic activities play pivotal roles in these transformations. This study systematically investigated Xinhui Chenpi aged 1–10 years to elucidate the dynamics of dominant fungal genera and experimentally verify their involvement in flavonoid transformation. Ultra-performance liquid chromatography (UPLC), third-generation full-length ITS sequencing (PacBio) , and strain isolation with culture assays were employed to characterize flavonoid profiles, fungal community succession, and the transformation capabilities of key isolates. Flavonoids exhibited a “degradation to resynthesis” trajectory, with polymethoxyflavones (PMFs) steadily accumulating throughout the aging process. Late-stage samples were dominated by the xerophilic genus Xeromyces (Aspergillaceae), which showed strong positive correlations with PMF enrichment, whereas correlations with Penicillium progressively declined over time. Importantly, Aspergillus tubingensis was isolated and confirmed to convert nobiletin into 3′-demethylnobiletin, providing direct mechanistic evidence for fungal-driven PMF structural modification. Community profiling further revealed that multiple Aspergillaceae genera ( Aspergillus , Penicillium , Xeromyces ) may participate in flavonoid transformation. These findings elucidate the microbial mechanisms underlying quality enhancement in aged Chenpi and provide a scientific basis for microbial-assisted optimization of modern aging processes, thereby offering theoretical support for the traditional principle that “aged Chenpi becomes more efficacious.”
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2024
·
IF 3.2
Xiaojie Fan,Jiaxin Guo,Dongyan Feng,Dahong Li,Huiming Hua
Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones , garpedunchromones A-C ( 1 – 3 ), and one biflavonoid , nujiangbiflavone A ( 14 ), along with fifteen known analogs ( 4 – 13 , 15 – 19 ) were isolated from G. pedunculata and G. nujiangensis . The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses , and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B ( 2 ) was the most active with an IC 50 value of 18.11 ± 0.96 μM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.
研究领域:
植物化学
·
药理学
·
天然产物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
·
2023
·Vol. 45
·期 10
·1355-1364
·
IF 2.7
Gao Yahui,Li Fen,Wang Yulu,Chen Zhou,Li Zijie
Purpose In our previous study, we constructed a one-pot multi-enzyme system for rare ketoses synthesis based on L-rhamnulose-1-phosphate aldolase (RhaD) from accessible glycerol in vitro. To eliminate tedious purification of enzymes, a facile Escherichia coli whole-cell cascade platform was established in this study. Methods To enhance the conversion rate, the reaction conditions, substrate concentrations and expressions of related enzymes were extensively optimized. Results The biosynthetic route for the cascade synthesis of rare ketoses in whole cells was successfully constructed and three rare ketoses including D-allulose, D-sorbose and L-fructose were produced using glycerol and D/L-glyceraldehyde (GA). Under optimized conditions, the conversion rates of rare ketoses were 85.0% and 93.0% using D-GA and L-GA as the receptor, respectively. Furthermore, alditol oxidase (AldO) was introduced to the whole-cell system to generate D-GA from glycerol, and the total production yield of D-sorbose and D-allulose was 8.2 g l −1 only from the sole carbon source glycerol. Conclusion This study demonstrates a feasible and cost-efficient method for rare sugars synthesis and can also be applied to the green synthesis of other value-added chemicals from glycerol.
研究领域:
生物化学
·
合成生物学
·
代谢工程
✓ 已验证
DOI
高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
·
2014
·Vol. 119
·期 3
·1913-1921
·
IF 2.206
Wang Hui,Wang Jun,Feng Tian-tian,Ramdani Noureddine,Li Yue,Xu Xiao-dong,Liu Wen-bin
A series of fluorene-based benzoxazine-endcapped copoly(ether ketone ketone)s (co-PEKKs) were successfully synthesized, in which the co-PEKKs were prepared with different molar ratios of 2,7-dihydroxy-9-fluorenone to bisphenol-A. The obtained phenol-ended co-PEKKs reacted with formaldehyde and n -butylamine to yield the benzoxazine-endcapped co-PEKKs (B-PEKKs). The structure of these oligomers was studied by Fourier transform infrared spectroscopy and 1 H nuclear magnetic resonance spectroscopy, and the molecular mass of these phenol-ended co-PEKKs was detected by gel permeation chromatography. The thermal behaviors of these B-PEKKs were determined by differential scanning calorimetry. In addition, the thermal and dynamic mechanical properties of the polymer films were investigated by thermogravimetric analysis and dynamic mechanical analysis. The results indicate that the incorporation of co-PEKKs within the benzoxazine backbone considerably improves the toughness of the fluorene-containing polybenzoxazines without much sacrifice of their thermal properties. Furthermore, as the content of 2,7-dihydroxy-9-fluorenone increases, the T
5 values decrease, while the T
g values and char yields of the prepared polymers increase to reach their highest values at 256 °C and 64 %, respectively.
研究领域:
材料科学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 47
·29752-29761
·
IF 3.361
Hong Chen,Fangsheng Wu,Yibing Xu,Yuan Liu,Lun Song,Xiujuan Chen,Qun He,Wei Liu,Qiaoying Han,Zihua Zhang,Yun Zou,Wenbin Liu
As a kind of new psychoactive substance (NPS), synthetic cathinones have drawn great worldwide attention. In this study, molecularly imprinted polymers (MIPs), as adsorbents for the extraction and determination of 4-methyldimethcathinone (4-MDMC), were first synthesized by coprecipitation polymerization. The physicochemical analyses of MIPs were successfully performed by XRD, FTIR, FESEM and TGA techniques. Furthermore, rebinding properties of temperature and pH dependence, and selectivity and reusability tests for MIPs and non-imprinted polymers (NIPs) were performed using an ultraviolet-visible spectrometer (UV-vis). The obtained results indicate that the imprinting efficiency has strong dependence on temperature and pH, and the optimal adsorption for targets is achieved under the condition of 318 K and pH = 6.0. This means that the combination between the polymers and 4-MDMC is a strong spontaneous and endothermic process. Compared with NIPs, MIPs exhibit prominent adsorption capacity (Qe = 9.77 mg g−1, 318 K). The selectivity coefficients (k) of MIPs for 4-MDMC, methylenedioxypentedrone (βk-MBDP), 4-ethylmethcathinone (4-EMC), methoxetamine (MXE) and tetrahydrofuranylfentanyl (THF-F) were found to be 1.70, 3.49, 7.14 and 5.82, respectively. Moreover, it was found that the adsorption equilibrium was achieved within 30 min. The aim of this work is the simple synthesis of MIPs and the optimal performance of the molecular recognition of 4-MDMC. Moreover, the synthesized MIPs can be easily regenerated and repeatedly used with negligible loss of efficiency (only 9.94% loss after six times adsorption–desorption tests). Satisfying recoveries in the range of 69.3–78.9% indicate that MIPs have good applicability for analyte removal from urine samples. Ultimately, this material shows great promise for the rapid extraction and separation of synthetic cathinones, which are dissolved in the liquid for the field of criminal sciences.
研究领域:
分析化学
·
法医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Wen-Juan Ma,Hua-Yu Chen,Yong-Liang Huang,Jia-Mei Chen,Tong-Bu Lu
This study is designed to compare drug encapsulation by cucurbit[7]uril and β-cyclodextrin, using fluorofenidone as a model drug. Single-crystal X-ray diffraction analysis was employed to successfully determine the crystal structures of fluorofenidone·H+@cucurbit[7]uril Form, fluorofenidone@cucurbit[7]uril Form, and fluorofenidone@β-cyclodextrin Form. Keto–enol tautomerization of fluorofenidone mediated by cucurbit[7]uril in acid solution is confirmed by crystal structures, pH titration, and nuclear magnetic resonance experiments. However, β-cyclodextrin cannot cause the keto–enol tautomerization of fluorofenidone under similar conditions. The phase solubility study demonstrates that cucurbit[7]uril has a much higher solubilization capacity for fluorofenidone than β-cyclodextrin in 0.1 M HCl since the Kc values of fluorofenidone with cucurbit[7]uril and β-cyclodextrin were 1223.97 ± 452.68 and 78.49 ± 10.56 M–1, respectively. Excellent solubility can be attributed to the keto–enol tautomerization of fluorofenidone under the conditions of cucurbit[7]uril in acid solution. The enol form of fluorofenidone is encapsulated by cucurbit[7]uril by hydrogen bonding interaction and hydrophobic interaction to increase binding affinity. Rat pharmacokinetic studies demonstrate that the area under the plasma concentration–time curve from time 0 to 7 h value of fluorofenidone@cucurbit[7]uril complex is 1.70-fold greater than that of free fluorofenidone, and the mean residence time from time 0 to 7 h is slightly prolonged from 1.29 to 1.76 h (P < 0.01) after oral administration. However, no significant difference is found between fluorofenidone and fluorofenidone@β-cyclodextrin complex. This work indicates that the induction of keto–enol tautomerization of drugs using macrocyclic molecules has the potential to be an effective method to improve their solubility and bioavailability, providing valuable insights for the application of macrocyclic molecules in the biomedical field.
研究领域:
药学
·
生物化学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Chemical Biology
·
2020
·
IF 7.739
Giorgia Croppi,Yueyang Zhou,Rong Yang,Yunfei Bian,Mingtao Zhao,Youtian Hu,Benfang Helen Ruan,Jing Yu,Fang Wu
Summary H 2 S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for Escherichia coli MST (eMST) through high-throughput screening of ∼26,000 compounds. The thiazolidinedione-type inhibitors were found to selectively bind to Arg178 and Ser239 residues of eMST but hardly affected human MST. Moreover, the pioglitazone of this class concentration dependently accumulates the 3-mercaptopyruvate substrate and suppresses the H 2 S and reactive sulfane sulfur products in bacteria. Importantly, pioglitazone could potentiate the level of reactive oxygen species in cellulo and consequently enhance the antimicrobial effects of gentamicin and macrophages in culture. This study has identified the bioactive inhibitor of eMST, paving the way for the pharmacological targeting of eMST to synergistically control the survival of E. coli .
研究领域:
微生物学
·
药理学
·
细菌致病机制
·
抗菌治疗
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 23
·13769-13779
·
IF 3.361
Yao Lu,Yi Xu,Meng-Ting Song,Ling-Ling Qian,Xiao-Lin Liu,Rong-Yao Gao,Rui-Min Han,Leif H. Skibsted,Jian-Ping Zhang
Tyrosinase, widely distributed in nature, is a copper-containing polyphenol oxidase involved in the formation of melanin. Flavonoids are most often considered as tyrosinase inhibitors but have also been confirmed to be tyrosinase substrates. Four structure-related flavonoids including flavones (apigenin and luteolin) and flavonols (kaempferol and quercetin) are found to promote not inhibit browning induced by tyrosinase catalyzed oxidation both in model systems and in mushrooms under aerobic conditions. A comparison with enzymatic oxidation and autooxidation of flavonoids alone has helped to clarify why flavonoids function as a substrate rather than an inhibitor. Flavonoids almost do not affect the kinetics of melanin formation from enzymatic oxidation of L-dopa in excess. In addition, a new brown complex formed during the reaction of flavonoid quinone and dopaquinone is suggested to enhance the browning effects by competing with isomerization and autooxidation. Structure–activity relationships of the four flavonoids in melanin formation leading to browning induced by autooxidation and enzymatic oxidation confirm the enzymatic nature of the browning.
研究领域:
生物化学
·
食品科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 18
·3904
·
IF 4.967
Xin Liu,Xiaozhou Zhang,Jiawei Jiang,Hongge Jia,Xigao Jian,Jinyan Wang
Polyether ketone (PEK) plastics are linear thermoplastic polymers connected by at least one ether bond and at least one ketone bond on the aryl group. The reason for their excellent heat resistance, rigidity, and mechanical strength is that their main molecular chain contains plenty of aromatic rings and polar carbonyl groups, and their molecular chain presents a large rigidity and strong intermolecular force. In addition, the main chain contains a considerable number of ether bonds, resulting in a certain toughness. However, polyether ketone materials have the disadvantage of poor solubility because of their excellent rigidity. To improve the solubility of polyether ketone, the preparation method of a novel nitrogenous heterocyclic polyaromatic ether monomer, 2-(4-chlorophenyl)-2,3-dihydrophthalazine-1,4-dione (CDD), was proposed, and its activity of polymerization was studied. The average molecular weight of the poly(aryl ether ketone) containing a nitrogenous heterocyclic polyaromatic ether group obtained by self-polycondensation of CDD was 4.181 × 103kg/mol, and the yield was 90.5%. In order to further explore the activity of monomers, novel copolymerized poly(aryl ether ketone) (PBCD) containing a nitrogenous heterocyclic polyaromatic ether structure was prepared by ternary copolymerization with 4,4-difluorobenzophenone (DFBP) and bisphenol fluorene (BHPF) with high activity. The average molecular weight of PBCD was 72.793 × 103kg/mol, the molecular weight distribution was 2.344, and the yield was 88.1%. Fourier transform infrared spectroscopy (FT-IR) and1H NMR were used to confirm the structure of the obtained polymer. Through thermogravimetric analysis (TGA), the determined weight loss temperature of 5% under nitrogen was higher than 500 °C, indicating excellent thermal stability. Compared with the solubility of the binary copolymer containing fluorenyl poly(aryl ether ketone) (PBD), the polymer showed reasonable solubility in selective solvents such as chloroform andN,N-dimethylacetamide.Keywords:poly(aryl ether ketone);solubility;thermal properties
研究领域:
高分子科学
·
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN FOOD RESEARCH AND TECHNOLOGY
·
2021
·Vol. 248
·期 2
·553-565
·
IF 2.998
Wang Liling,Qin Yuchuan,Wang Yanbin,Liu Bentong,Zhou Yifeng
In this research, the inhibition mechanism of a pairs of homoisoflavonoid analogues (6-aldehydo-isoophiopogonanone A (AIO-A) and 6-aldehydo-isoophiopogonanone B (AIO-B)) on tyrosinase (Tyr) was investigated by multi-spectroscopic techniques combined with molecular docking. The results demonstrated that AIO-A suppressed the activity of Tyr in a reversible competitive-inhibition with a half inhibitory concentration (IC50) of (12.67 ± 2.52) × 10 –5 molˑL −1 , while AIO-B was a reversible mixed-inhibition with IC50 of (4.81 ± 0.74) × 10 –5 molˑL −1 . AIO-A/AIO-B bound to Tyr driven by the intermolecular interactions, including van der Waals interaction, hydrogen bonding and hydrophobic interaction, thereby resulted in a secondary structure change of Tyr and its intrinsic fluorescence quenching. The molecular docking revealed that an aldehyde oxygen atom in AIO-A and methoxyphenyl in AIO-B formed coordination with two Cu ions in the active center of Tyr protein. It can be deduced that the coordination with two Cu ions may prevent the entrance of substrate and then inhibit the catalytic activity of Tyr. The research might provide new perspectives on the inhibition mechanism of AIO-A and AIO-B on Tyr and functional research for the prevention and treatment of pigmented skin diseases and anti-browning of homoisoflavonoids as a food supplement.
研究领域:
生物化学
·
药理学
·
植物化学
✓ 已验证
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yabing Shan,Jiayi Li,Ying Chen,Dongmei Li,Yanbo Luo,Yongqiang Pang,Di Chen
The illegal addition of androgenic steroids, such as testosterone and methyltestosterone, to herbal oral liquids poses a significant threat to consumer health. This study presents a novel method for the extraction and determination of these steroids in herbal products using pipette tip solid-phase microextraction combined with liquid chromatography-tandem mass spectrometry. The pipette tips are coated with hydroxyl-functionalized multi-walled carbon nanotubes, ensuring efficient analyte extraction while reducing sample handling and contamination risks. The method was optimized for parameters such as solvent volume, extraction time, and pH, and demonstrated excellent analytical performance. It demonstrated linearity over the range of 5–5000 ng/mL (R 2 > 0.99), with detection limits of 0.96 ng/mL for testosterone and 1.44 ng/mL for methyltestosterone, and limits of quantification of 3.20 ng/mL for testosterone and 4.80 ng/mL for methyltestosterone. Recovery experiments across multiple matrices and concentration levels showed recoveries ranging from 93.8 % to 108.1 %, with relative standard deviations between 1.1 % and 4.5 %. This approach offers a cost-effective, high-throughput solution for the routine detection of illegal steroid additives in herbal and functional food products, providing a valuable tool for regulatory monitoring and consumer safety.
研究领域:
分析化学
·
食品安全
·
药物分析
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）