CHEMISTRY & BIODIVERSITY
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2021
·Vol. 19
·期 1
·e202100740
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IF 2.408
Xiang Liu,Jinqiu Rao,Kai Wang,Meijun Wang,Tie Yao,Feng Qiu
Many stilbene glycosides can alleviate skin hyperpigmentation due to their inhibitory effect on tyrosinase. Mulberrosides in Morus alba L. are stilbene glycosides. In the present study, the inhibition of tyrosinase by five mulberrosides (S1–5), isolated from Morus alba L. was investigated and compared, and the inhibitory mechanism was explored. These five mulberrosides exhibited obvious inhibitory effects on tyrosinase only in a concentration-dependent manner, without time-dependence, indicating that they are reversible inhibitors of tyrosinase. S2, S1 and S5 inhibited tyrosinase activity with IC 50 values of 28.93, 75.94 and 151.72 μM, respectively, and were more active than kojic acid (IC 50 =169.13 μM). Kinetic studies revealed that S1, S2 and S4 were competitive inhibitors, while S3 and S5 were mixed inhibitors. Analysis of the fluorescent spectra showed that mulberrosides S1, S2 and S4 quenched the intrinsic fluorescence intensity of tyrosinase. A molecular docking study indicated that the interaction of tyrosinase with mulberrosides was reflected by compound scores as follows: S2>S5>S1>S3/S4>kojic acid, and hydroxy groups in the side chain of mulberrosides may play a crucial role in the binding of the enzyme. Our results suggest that mulberrosides in Morus alba L. could be further developed as whitening agents for enhanced performance against hyperpigmentation. Graphical
研究领域:
植物化学
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生物化学
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药理学
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DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2021
·
IF 5.645
Huan Wang,Chao Lei,Yunhang Zeng,Ying Song,Qixian Zhang,Bi Shi
Trypsin is used to remove non-collagenous proteins from cattle hide in leather processing but prone to damage hide surface and reduce leather quality due to its rapid protein hydrolysis action on the hide surface and slow penetration through the whole hide. A novel trypsin bating method was developed using a reversible inhibition of trypsin with high-yield, low-cost and environment-friendly soybean flour (SF). When the mass ratio of trypsin to SF was 1:20, the trypsin activity was decreased by 77 % at a reaction time of 5 min and completely returned in 100 min because of the competitive Kunitz trypsin inhibitor in SF. Bating with trypsin-SF mixture avoided the damage to hide surface caused by trypsin, improved the dispersion uniformity of hide collagen fibers and increased the softness and the mechanical strength of leather. This work exhibits huge potential for improving the leather quality and provides new insights into the soybean application.
研究领域:
生物化学
·
皮革加工
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环境科学
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产品关联
DOI
高影响因子
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
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生物化学
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DOI
高影响因子
FOOD CHEMISTRY
·
2015
·
IF 3.391
Lei Zhou,Wei Liu,Zhiqiang Xiong,Liqiang Zou,Jun Chen,Junping Liu,Junzhen Zhong
It is still unclear whether the inhibitory effect of organic acid on polyphenoloxidase (PPO) is due to the reversible inhibition or decrease of pH. In this study, cinnamic acid, citric acid and malic acid inhibited PPO in different modes. Results showed that the inhibition by cinnamic acid resulted from reversible inhibition, while the decrease of pH was the main cause for citric acid and malic acid. The kinetic results showed that cinnamic acid reversibly inhibited PPO in a mixed-type manner. Fluorescence emission spectra indicated that cinnamic acid might interact with PPO and quench its intrinsic fluorescence, while the decrease of the fluorescence intensity induced by citric acid or malic acid was due to the acid-pH. Cinnamic acid bound to PPO and induced the rearrangement of secondary structure. Molecular docking result revealed cinnamic acid inserted into the hydrophobic cavity of PPO by forming π–π stacking.
研究领域:
生物化学
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食品科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2024
·Vol. 59
·期 3
·1761-1769
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IF 2.6
Jing Zhao,Wenwei Chen,Hua Liu,Xiaosan Zhang,Fei Tao,Zhenbao Jia
Summary Inhibition of α-glucosidases is recognised as an effective approach towards managing postprandial hyperglycaemia. This study aimed to identify a specific compound in Carya cathayensis Sarg. kernels (CCSKs) exhibiting strong inhibitory activities against α-glucosidase and elucidate the inhibitory kinetic mechanism. Employing a bioassay-guided approach, an α-glucosidase inhibitor was isolated from CCSKs through sequential chromatography protocol involving AB-8 macroporous adsorptive resin, Sephadex LH-20 and C 18 -reversed phase silica gel. The resulting inhibitor was a novel tannin compound, identified as rugosin C ethyl ester. Rugosin C ethyl ester displayed superior inhibitory activity (IC 50 of 2.60 μg/mL) compared to acarbose (IC 50 of 105.95 μg/mL). The kinetic analysis indicated that rugosin C ethyl ester had a mixed-type reversible inhibition against α-glucosidase. The inhibition constants ( K i and K is ) were determined to be 3.119 and 0.856 μg/mL, respectively. The findings indicated that rugosin C ethyl ester might serve as a promising functional ingredient in low-glycemic index foods.
研究领域:
食品科学
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植物化学
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药理学
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DOI
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2020
·Vol. 29
·期 7
·1230-1237
·
IF 1.783
Jiang Tingting,Cheng Ting,Li Jing,Zhou Mengyue,Tan Rong,Yang Xiaojing,Wang Yang,Li Weiwei,Zheng Jiang
Grapefruit-mediated fruit–drug interaction has been well discussed in clinical practice. However, the biochemical mechanisms for such interaction are far beyond our understanding. The objectives of the present study aimed at the interaction between bergaptol (BGT) and CYP2C9. BGT, one of the major furanocoumarin constituents in grapefruit, has been reported to inhibit the activity of CYP2C9. And a number of furan-containing compounds are known to act as mechanism-based inactivators of CYP2C9. In this study, BGT was found to induce time-, concentration-, and NADPH-dependent irreversible inhibition of CYP2C9. A GSH conjugate was detected in an incubation mixture containing CYP2C9, BGT, NADPH, and GSH. Further mechanistic investigation revealed that a γ-ketoenal metabolite was responsible for the enzyme inactivation. The obtained data indicate that BGT was a mechanism-based inactivator of CYP2C9. The study would facilitate the understanding of the mechanistic insight into fruit–drug interactions mediated by grapefruits.
研究领域:
药理学
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生物化学
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临床药理学
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产品关联
DOI
高影响因子
STAR Protocols
·
2024
·
IF 1.3
Shibo Sun,Haowen Liu,Wuyang Shi,Hanziyi Zhou,Hao Wu,Weiping Xu,Jianqiang Xu
Summary Selenoprotein thioredoxin reductase 1 (TXNRD1) is a promising therapeutic target, with several inhibitors reported to inhibit TXNRD1 activity. These inhibitors have the potential for applications such as anti-tumor medications. Here, we present a protocol for assessing irreversible inhibitors of TXNRD1. We describe four assays covering cellular TXNRD activity measurement, recombinant enzyme-based activity determination, differential scanning fluorimetry (DSF), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This protocol will facilitate the screening and development of potential small-molecule inhibitors of TXNRD1.
研究领域:
药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 84
·期 9
·1788-1798
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IF 1.516
Liu Feng,Xu Wen-Fei,Mu Hang,Lv Zhi-Rong,Peng Jie,Guo Chao,Zhou Hai-Meng,Ye Zhuo-Ming,Li Xu-Hui
Many phenolic compounds, derived from lignin during the pretreatment of lignocellulosic biomass, could obviously inhibit the activity of cellulolytic and hemicellulolytic enzymes. Acetosyringone (AS) is one of the phenolic compounds produced from lignin degradation. In this study, we investigated the inhibitory effects of AS on xylanase activity through kinetic experiments. The results showed that AS could obviously inhibit the activity of xylanase in a reversible and noncompetitive binding manner (up to 50% activity loss). Inhibitory kinetics and constants of xylanase on AS were conducted by the HCH-1 model (β = 0.0090 ± 0.0009 mM−1). Furthermore, intrinsic and 8-anilino-1-naphthalenesulfonic (ANS)-binding fluorescence results showed that the tertiary structure of AS-mediated xylanase was altered. These findings provide new insights into the role of AS in xylanase activity. Our results also suggest that AS was an inhibitor of xylanase and targeting AS was a potential strategy to increase xylose production.
研究领域:
生物化学
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酶学
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生物技术
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2012
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IF 2.865
Xingguo Tian,Erqun Song,Ruxian Pi,Xiaokang Zhu,Lichao Liu,Xiaoyan Ma,Hui Dong,Jing Liu,Yang Song
Research on the effects of polychlorinated biphenyl (PCB) toxicity tends to focus on commercial PCB congeners and parent PCBs themselves. However, studies have suggested that PCB metabolites may be more interesting than the parent compounds because of their high reactivity. As a key metabolic enzyme, glutathione S -transferases (GSTs) are responsible for detoxification by catalyzing the conjugation reaction of glutathione (GSH) to xenobiotics. Inhibition of GST activity indicates reduced detoxification ability. We investigated the inhibition of chicken liver GSTs by parent PCBs and their metabolites and observed dose-dependent inhibition in vitro ; inhibitory efficiency declined in the order GSH-conjugate > mono-hydroxyl ≈ quinone ≈ hydroquinone > parent PCB. Structure–inhibitory activity relationship studies indicated that with the inhibitory activity greatly increases with the number of GSH moieties or chlorine substituents on the quinone ring. However, no significant linear relationship was observed for chlorine pattern changes on the phenyl ring. The reversibility of PCB metabolite inhibition of GSTs is discussed. PCB mono-hydroxyl, hydroquinone and quinone forms showed irreversible inhibition of GSTs, which suggests a mechanism involving covalent binding to cysteine residues in the GST active site. PCB glutathionyl conjugates showed reversible GST inhibition, implying non-covalent binding. Furthermore, reactive oxygen species did not significantly affect GST activity.
研究领域:
环境毒理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Jianxia Zhang,Yi Wang,Mengying Wang,Peipei Wang,Hao Yan,Dalong Wang,Jiahao Zheng,Bin Li,Chaoyue Chen,Di Cao,Xiaohui Zheng,Xiaokun Li,Kun Wang,Zhiguo Liu
Fibroblast growth factor receptors (FGFRs) play a critical role in the regulation of cancer cell proliferation, differentiation, and migration. However, the development of acquired resistance to FGFR inhibitors remains a major challenge in treating non-small cell lung cancer (NSCLC), particularly due to mutations at the gatekeeper residue. In this study, we report the discovery of a series of irreversible FGFR inhibitors targeting gatekeeper mutations in FGFR1–3, utilizing a 2,4,5-trisubstituted pyrimidine scaffold. Through rational design, structure–activity relationship optimization, and pharmacokinetic evaluation, compound ng 12l emerged as a promising candidate. It demonstrated potent inhibition of FGFR1–3 gatekeeper mutations in vitro along with favorable pharmacokinetic properties. The efficacy of 12l in targeting FGFR1 gatekeeper mutations was confirmed in assays using L6-FGFR1V561M/F cells. Furthermore, in xenograft models using both H1581 and L6-FGFR1V561M cells, 12l exhibited robust anti-tumor activity with minimal toxicity. These findings position 12l as a promising therapeutic agent for overcoming gatekeeper-mediated resistance in NSCLC.
研究领域:
肿瘤学
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药物化学
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药理学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 7
·1101-1110
·
IF 5.064
Ma Xiao-yao,Zhang Man,Fang Ge,Cheng Chuan-jing,Wang Mu-kuo,Han Yi-man,Hou Xiao-tao,Hao Er-wei,Hou Yuan-yuan,Bai Gang
Alcoholic liver disease (ALD) is one of the pathogenic factors of chronic liver disease with the highest clinical morbidity worldwide. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, has shown many health benefits including antioxidative, anti-inflammatory, anticancer, and hepatoprotective activities. We previously found that UA was metabolized in vivo into epoxy-modified UA containing an epoxy electrophilic group and had the potential to react with nucleophilic groups. In this study we prepared an alkynyl-modified UA (AM-UA) probe for tracing and capturing the target protein of UA from liver in mice, then investigated the mode by which UA bound to its target in vivo. By conducting proteome identification and bioinformatics analysis, we identified caspase-3 (CASP3) as the primary target protein of UA associated with liver protection. Molecule docking analysis showed that the epoxy group of the UA metabolite reacted with Cys-163 of CASP3, forming a covalent bond with CASP3. The binding mode of the UA metabolites (UA, CM-UA, and EM-UA) was verified by biochemical evaluation, demonstrating that the epoxy group produced by metabolism played an important role in the inhibition of CASP3. In alcohol-treated HepG2 cells, pretreatment with the UA metabolite (10 μM) irreversibly inhibited CASP3 activities, and subsequently decreased the cleavage of PARP and cell apoptosis. Finally, pre-administration of UA (20–80 mg· kg −1 per day, ig, for 1 week) dose-dependently alleviated alcohol-induced liver injury in mice mainly via the inhibition of CASP3. In conclusion, this study demonstrates that UA is a valuable lead compound for the treatment of ALD.
研究领域:
药理学
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肝病学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）