JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2021
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IF 3.205
Hui-Peng Song,Hui Zhang,Rui Hu,Hong-He Xiao,Hua Guo,Wei-Hong Yuan,Xin-Tong Han,Xin-Yi Xu,Xin Zhang,Zi-Xuan Ding,Ming-Yue Zhao,Ting-Guo Kang,Hui-Yang Sun,An Chang,Yue-Hua Chen,Ming Xie
Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC 50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC 50 values. The structure–activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of “stem is the medicinal part of Mahonia bealei and Mahonia fortunei ”. Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.
研究领域:
药理学
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中药学
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药物发现
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天然产物化学
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DOI
PubMed
高影响因子
Analytical Methods
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2015
·Vol. 7
·期 23
·9984-9991
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IF 1.821
Qingming Zhang,Xue Li,Bingchen Li,Huanshun Yin,Shiyun Ai
A sensitive and selective electrochemical biosensor was fabricated for polynucleotide kinase (PNK) activity assay and inhibitor screening based on phos-tag-biotin mediated double signal amplification, where streptavidin and alkaline phosphatase-conjugated biotin (biotin-ALP) were used as the signal amplification units. After the immobilization of probe DNA on the electrode surface, it was hybridized with complementary DNA containing the 5′-OH terminal, the OH can be phosphorylated under the catalytic effect of PNK in the presence of ATP. The generated phosphate group at the 5′-terminal can be further recognized by phos-tag-biotin, where phos-tag-biotin was not only used as the specific recognition reagent for the phosphate group, but also the capture reagent for streptavidin to induce the further assembly of biotin-ALP. Under the catalytic effect of ALP, the substrate of p-nitrophenyl phosphate disodium salt hexahydrate (PNPP) can be hydrolyzed to produce p-nitrophenol (PNP). According to the relationship between the electrochemical response of PNP and the logarithmic value of PNK concentration, a linear range of 0.01–5 units per mL and a low detection limit of 0.0027 unit per mL were achieved. The developed method showed high selectivity. The inhibition effect of (NH4)2SO4 and Na2HPO4 was also evaluated and the IC50 values were calculated.
研究领域:
生物化学
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分析化学
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电化学
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分子生物学
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DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2023
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IF 3.8
Hai-Xia Xu,Hui Chen,Zhong-Ping Yin,Qing-Feng Zhang
s Inhibition of α-glucosidase and non-enzymatic glycation is an effective approach to treat type 2 diabetes. Piceid (PI) is a potential α-glucosidase inhibitor and antiglycation agent found in many plant-based foods and herbs. To enhance the liposolubility and hypoglycemic effects of PI, two PI dicarboxylic acid esters were synthesized via enzymatic acylation in green solvents using dicarboxylic acids with hypoglycemic activity as acyl donors. Their structures were characterized by HPLC, HRMS, and 13 C NMR. Also, the antiglycation and α-glucosidase inhibitory effects of PI derivatives were investigated by enzymatic kinetics, CD, bovine serum albumin (BSA)-fructose model, FTIR, and molecular docking analysis. The results found that the introduction of dicarboxylic acid molecules significantly enhanced liposolubility, antiglycation, and α-glucosidase inhibitory activities of PI. The IC 50 values of two PI derivatives on α-glucosidase were nearly 9.9-fold and 16.2-fold lower than native PI, respectively. Moreover, the dicarboxylic acid moieties in PI derivatives induced the conformational changes of α-glucosidase, which made the secondary structure of α-glucosidase tighter, thus hindering the entry of substrates. Molecular docking results showed that PI derivatives could insert into the active pocket of α-glucosidase and interact with more key amino acid residues than PI. Also, PI derivatives could block the glycation sites of BSA.
研究领域:
药理学
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化学
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生物化学
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分子生物学
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糖尿病研究
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DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Wen Li,Xinyue Cui,Zilin Chen
An online capillary electrophoresis method based-lipase immobilized enzyme microreactor was developed for lipase kinetic study and inhibitor screening from compounds from natural products. Zeolitic Imidazolate Framework-8 (ZIF-8) has the advantages of large pore size, mild synthesis conditions and good biocompatibility. Lipase was immobilized on the inner wall of capillary with the help of the metal-organic framework ZIF-8. The results of electron microscopy showed that lipase could be aggregated and fixed on the inner wall of capillary by ZIF-8. After the experimental conditions including electrophoretic separation and enzymatic reaction were optimized, the baseline separation of substrate p-nitrophenyl acetate (pNPA) and product p-nitrophenol (pNP) was achieved within 3 min. The immobilized enzyme microreactor showed good repeatability and stability, and the determined Michaelis-Menten constant ( K m ) of lipase was 2.75 mM, which was lower than the kinetic constant determined in off-line reaction, indicating that the immobilized enzyme had a high affinity with the substrate. In addition, the IC 50 value of the positive control compound orlistat on lipase inhibition was 7.26 nM, which was consistent with the literature. Then the inhibitory activity of 10 compounds from natural products on lipase was evaluated by the ZIF-8-IMER. Among them, 7 compounds including baicalein, luteolin, epicatechin gallic acid, and chlorogenic acid, had a certain inhibitory effect on lipase. The molecular docking technology proved the interaction between the enzyme and the screened inhibitor, which provides a new method for the screening of lipase inhibitors.
研究领域:
生物化学
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分析化学
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药学
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酶学
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DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2024
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IF 3.8
Wujiu Jiang,Qing Luo,Wei Huang,Yuxing Tan,Yiyuan Peng
Diorganotin acylhydrazone complexes with mitochondrial targeting demonstrate significant potential as replacements for platinum-based complexes due to their potent anticancer properties. Twelve methylphenyltin arylformylhydrazone complexes have been synthesized by microwave “one-pot” reaction. The complexes have been characterized by FT-IR, multinuclear NMR ( 1 H, 13 C, and 119 Sn), TGA, and HRMS. Crystal structures were determined for 10 out of the 12 complexes under study. Structures 1 through 8 , 10 and 12 possessed a central symmetric structure of a di-nuclear Sn 2 O 2 tetrahedral ring. All complexes were tested for their inhibitory activity against human cell lines NCI-H460, MCF-7, and HepG2. Complex 8 exhibited the most effective inhibitory effect on HepG2 cells, with an IC 50 value of 1.34 ± 0.04 μM. Preliminary studies on the anticancer mechanism suggest that complex 8 induces apoptosis in HepG2 cells via the mitochondrial pathway, accompanied by G2/M phase cell cycle arrest.
研究领域:
无机化学
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药物化学
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癌症研究
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药学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yuanyuan Zhao,Junjie Gong,Hanwen Liu,Huimin Huang,Wen-song Tan,Haibo Cai
Liver cancer organoids replicate the pathophysiology of primary tumors, making them ideal for drug screening and efficacy evaluation. However, their growth in complex, variable, animal-derived matrices hinders practical application. Here, we designed an easily accessible, chemically defined, biocompatible double-network hydrogel (HADR) using methacrylated hyaluronic acid (HAMA), sodium alginate (SA), methacrylamide dopamine (DMA), and c(RGDFC) for liver cancer organoid culture. By optimizing critical extracellular matrix (ECM) parameters, the HADR hydrogel achieves compatibility with the physiological mechanics of the human liver and fosters the adhesion and proliferation of multiple cell types. In vitro drug efficacy tests showed that HepG 2 cell line-derived liver cancer organoids exhibited higher IC50 values than 2D cultures, indicating greater drug resistance. Subcutaneous tumor models in nude mice revealed that HADR hydrogels created a microenvironment for HepG 2 cells mirroring the natural tumor ECM, leading to increased tumor volume, denser cell arrangement, and concurrent microvascular development. In vivo drug efficacy evaluations indicated that DOX treatment downregulated Ki-67 and MMP-9 expression, inhibiting HepG 2 cell proliferation, invasion, and metastasis. These findings demonstrate the potential of HADR hydrogels for liver cancer organoid culture, offering new strategies for personalized drug screening and efficacy evaluation.
研究领域:
生物医学工程
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组织工程
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癌症生物学
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药学
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生物材料
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2019
·Vol. 43
·期 11
·e13028
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IF 1.358
Meiling Han,Ai Li,Ting Shen,Jiaxin Meng,Yongqin Lei,Xian Zhang,Pengyuan Liu,Linxin Gan,Lei Ao,Houhua Li
The study aims to analyze the phenolic compounds in Malus spp. and evaluate their antioxidant and pro-apoptotic effects in BGC-803 gastric cancer cells. The results showed that cyanidin-3-galactoside was the main polyphenol in Malus “Royalty” (MR), while catechin, epicatechin, and proanthocyanidin B1 and B2 contents were higher in Malus “Cinnabar” (MC) and Malus micromalus (MM) than in MR fruits. The total polyphenol content, total flavonoid content, and antioxidative properties of Malus spp. fruits followed an order of MR > MC > MM. Fruit extracts could inhibit BGC-803 cells growth and induce apoptosis, with IC 50 values of 0.47, 0.36, and 0.31 mg/ml for MR, MC, and MM, respectively. Furthermore, fruit extracts induced cell apoptosis through increasing Bcl-2 and Bcl-xl (pro-apoptosis) expression and inhibiting Bax and Bak (anti-apoptosis) expression, thereby accelerating cell apoptosis. Taken together, these results demonstrate that red fruits (i.e., MR and MC) were more effective against cancer cells than green fruits (i.e., MM). Practical applications Fruits of Malus spp. are ≤5 cm in size, considerably smaller than apples. They are rich in various natural bioactive compounds that are often consumed as a dietary supplement or used as natural raw materials for function food. In the current study, it is comprehensively characterized profile and bioactivity of phenolic metabolites in Malus spp. fruits of different colors, and found that red fruits are more effective in reducing the free radicals and inducing cancer cells apoptosis than green fruits. These findings are valuable for food technologists and food manufacturers, especially those who produce crabapple supplement. The study investigated the molecular mechanism of how Malus spp. fruits exert anti-cancer functions. This lays a theoretical foundation for future research on developing anti-cancer function food and provides helpful guidance for fruit market management and fruit processing industry.
研究领域:
药理学
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肿瘤学
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食品科学
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植物科学
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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）