JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2021
·
IF 5.051
Xiang Zhou,Jiamin Liu,Jiao Meng,Yihong Fu,Zhibin Wu,Guiping Ouyang,Zhenchao Wang
Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro. Proliferation assays identified I20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I20 and tubulin Arg β369, which is also the binding site for the anticancer drug Taxol. Our results suggest that (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.
研究领域:
肿瘤学
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分子生物学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2018
·Vol. 143
·期 20
·5054-5060
·
IF 3.864
Bo Lin,Li Fan,Jinyin Ge,Wenjia Zhang,Caihong Zhang,Chuan Dong,Shaomin Shuang
A mitochondrial-targeted pH fluorescent probe 4-(2-(6-hydroxynaphthalen-2-yl)vinyl)-1-methylpyridin-1-ium was facilely synthesized via the carbon–carbon double bond bridging of 6-hydroxy-2-naphthaldehyde and 1,4-dimethylpyridinium iodide salt. The probe exhibited remarkable pH-dependent behavior in the linear range of 7.60–10.00, with a pKa value of 8.85 ± 0.04 near mitochondrial pH. A significantly large Stokes shift of 196 nm was obtained, which reduces the interference of excitation light. Application of the probe in live HepG2 cells indicated that the probe had excellent mitochondrial targeting ability and was successfully used to visualize mitochondrial pH fluctuations in live cells.
研究领域:
化学
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生物化学
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细胞生物学
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荧光成像
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Hai Shi,Mengjiao Wang,Youjing Gong,Yue Huang,Limin Ning,Yang Xiang,Yongmei Yin,Genxi Li
Phenotypic plasticity is an emerging paradigm for providing biological and clinical insights into cancer initiation, progression, and resistance to therapy. However, it is a great challenge to track phenotypic information on live cells with high levels of sensitivity, specificity, and simplicity, when a specific cancer-cell subset is being targeted. In this work, we have successfully achieved cascade assembly of nanoparticles on the surface of specific cancer cells by designing a dual-aptamer-weaved molecular AND logic system. Taking advantage of spatial addressability, precise controllability, and targeting recognition of the nanostructure assemblies, we can precisely label the target-cell subset in a large population of similar cells and rapidly obtain phenotypic information in response to the surface changes of captured cancer cells. Without sophisticated instruments, we can know the phenotypic information on HepG2 cells in whole blood with a high level of sensitivity and rapid naked-eye tracking of on-cell phenotype changes of HepG2 cells undergoing epithelial–mesenchymal transition.
研究领域:
癌症生物学
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纳米技术
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2014
·Vol. 10
·期 6
·948-958
·
IF 7.578
Liu Yongjun,Liu Chunxi,Li Min,Liu Fengxi,Feng Lixia,Zhang Li,Zhang Na
Multifunctional nanoparticles assembled from multi-block polymers are now one of the most convenient and convincing carriers for target drug delivery. Multi-block polymers could provide multi-functions such as sufficient drug loading capability and efficient target ligand coupling potency.
In this article, novel multi-block polymer poly(lactic acid)–poly(ethylene glycol)–poly(L-lysine) (PLA-PEG-PLL) with relatively precise block molecular weight were synthesized by new method which we called polymer–polymer conjugation. This method conjugated different polymer
blocks by reactions between the terminal active groups of different blocks, thus simplified the synthesis procedure. The obtained PLA-PEG-PLL was characterized by 1H NMR and gel permeation chromatography. The controlled drug delivery capability and the target ligand coupling potency
of PLA-PEG-PLL were verified using paclitaxel (PTX) as model drug and vascular endothelial growth factor (VEGF) antibody as target ligand. The PTX-loaded PLA-PEG-PLL nanoparticles (PNP) and VEGF antibody modified PTX-loaded PLA-PEG-PLL nanoparticles (VPNP) were prepared using solvent diffusion
methods. The two nanoparticles showed spherical or ellipsoidal shapes with uniform particle size distribution (190.1 ± 1.27 nm and 203.6 ± 4.10 nm for PNP and VPNP, respectively) and positive zeta potential (23.76 ± 0.72 mv and 20.76 ± 0.34 mv for PNP and VPNP,
respectively). The cellular cytotoxicity, cellular uptake, in vivo therapeutic effects of the two nanoparticles were investigated. Cytotoxicity of VPNP against HepG2 cells was superior to that of PNP and Taxol®. The VPNP and PNP showed better antitumor efficacy in a murine model
bearing H22 compared with Taxol® and VPNP was the best. The study on cellular uptake indicated that the better antitumor efficacy of VPNP was attributed to the increased uptake of drug by tumor cells. These results demonstrated that PLA-PEG-PLL was a favorable multifunctional
material for drug target delivery and polymer–polymer conjugation was a promising method to fabricate novel multi-block polymers.
研究领域:
药学
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纳米技术
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药物递送系统
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2019
·
IF 3.926
Ya-Liang Zhang,Rong Yang,Lin-Ying Xia,Ruo-Jun Man,Yi-Chun Chu,Ai-Qin Jiang,Zhong-Chang Wang,Hai-Liang Zhu
Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI 50 = 0.71–2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC 50 > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC 50 = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.
研究领域:
药理学
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癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2021
·
IF 4.952
Yin Zheng,Li Li,Zekun Jin,Peipei An,Shang-Tian Yang,Yongtao Fei,Gongliang Liu
The use of Schleiferilactobacillus ( S. ) harbinensis M1 as a starter culture, has been shown to improve the organoleptic quality of fermented soymilk, but its contribution to nutrient transformation and health-related functionality remains unclear. This study characterized the biotransformation of carbohydrates, isoflavones , proteins and free amino acids, as well as the antioxidant and antiproliferative activities of soymilk fermented by S. harbinensis M1. After fermentation, soybean carbohydrates were mainly converted into lactic acid (76.68 mmol/L) and acetic acid (8.19 mmol/L), isoflavone glucosides (daidzin and genistin) were partially converted to aglycones (daidzein and genistein). Soybean proteins were extensively hydrolyzed into oligopeptides and free amino acids, and the soluble peptide fraction (451-189 Da) increased from 4.6% to 86%. Whole-genome sequencing of S. harbinensis M1 revealed a 3,592,195 bp circular chromosome with 53.02% (G + C) content and 3375 coding genes. Metabolic prediction revealed the enzymes required for carbohydrate/pyruvate metabolism and isoflavone biotransformation. The whole proteolytic system was predicted, including peptide transport system and 66 genes encoding proteinases/peptidases. S. harbinensis M1 significantly ( p < 0.05) improved the antioxidant activity and antiproliferative effects of soymilk against HepG2/MCF-7 cells. These findings suggest that S. harbinensis M1 can be used as a proteolytic starter-culture to make functional fermented foods .
研究领域:
食品科学
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微生物学
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基因组学
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营养学
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生物化学
✓ 已验证
DOI
高影响因子
JOURNAL OF MICROENCAPSULATION
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2021
·
IF 3.142
Zhumei Ge,Qilong Wang,Qin Zhu,Mukhtar Yusif,Jiangnan Yu,Ximing Xu
Herein, a nano-micelle drug delivery system was developed to orally improved zingerone’s bioavailability and its antitumor effect. Indeed, zingerone-loaded d-α-tocopheryl polyethylene glycol succinate micelles (ZTMs) were effectively prepared, characterised and assessed. The ZTMs had diameter, polydispersity index, and zeta potential of 50.62 ± 0.25 nm, 0.168 ± 0.006, and −28.07 ± 0.33 mV, respectively, coupled with a high entrapment efficiency (m/m, %) were 94.71 ± 2.02. The release rate of ZTMs in three media was significantly greater than that of free zingerone. Intriguingly, results obtained from pharmacokinetic studies showed that the oral bioavailability of the ZTMs was enhanced by 5.10 times in comparison with the free zingerone. Further, the half inhibitory concentration (IC50) of ZTMs and free zingerone was 7.56 μg/ml and 14.30 μg/ml, respectively, on HepG2 cells. Hence, ZTMs may be used as a potential approach to enrich the solubility, bioavailability, and concomitant anti-proliferative effect of zingerone in vitro.
研究领域:
药学
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纳米技术
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药物递送系统
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Yang Zhang,Shan Zhao,Huayu Wang,Chunpo Ge
Cysteine (Cys), a pivotal biothiol involved in protein synthesis, metabolism, and detoxification, plays essential roles in various physiological and pathological processes. Dysregulation of Cys levels is associated with diseases such as Parkinson's, Alzheimer's, cardiovascular conditions, and hepatic pathologies. Despite advancements in Cys detection, probes specifically designed for lipid droplet (LD)-targeted Cys monitoring remain scarce. Here, we report the development of a fluorescent probe, DCI-HBT-Cys , for the selective detection of Cys within LDs. The probe features an acrylate-based recognition unit for specific nucleophilic cyclization with Cys and a hydrophobic DCI-HBT-OH fluorophore enabling efficient LD localization. DCI-HBT-Cys exhibits remarkable properties, including high selectivity, a large Stokes shift (240 nm), excellent photostability, and pH stability in the physiological range (pH 6–9). In vitro and cellular assays demonstrate the probe's ability to sensitively detect endogenous and exogenous Cys with minimal interference from related biothiols (e.g., Hcy, GSH). Furthermore, DCI-HBT-Cys enables real-time imaging of Cys upregulation in various cell lines, including HeLa and HepG2 cells, in response to ginseng polysaccharide stimulation. Co-localization studies confirm the probe’s LD-targeting specificity, while quantitative fluorescence analysis highlights its potential for precise Cys monitoring. These findings underscore the utility of DCI-HBT-Cys as a powerful tool for elucidating the intricate interplay between Cys metabolism, oxidative stress, and LD-associated cellular processes, paving the way for novel diagnostic and therapeutic strategies.
研究领域:
分析化学
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生物化学
·
细胞生物学
·
荧光成像
·
医学诊断
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Junjie Wang,Hui Zhou,Yang Li,Yeshu Mu,Jinghua Li,Chen Hong,Wen Luo
A novel series of benzo[ cd ]indol-2(1 H )-one-donepezil (BIO-DPZ) hybrids (5a-m, 6a-k) was designed, synthesized and evaluated as cholinesterase inhibitors and living cell imaging agents. These compounds were potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compound 6a exhibited the strongest inhibitory activity against AChE with an IC 50 value of 0.16 μM. Compound 6i had the strongest inhibition of BuChE with an IC 50 value of 5.37 μM. Kinetic and molecular modeling studies showed that 6a bound both catalytic active site and peripheral anionic site of AChE. Compounds 6a and 6i both showed lower SH-SY5Y, HepG2 and HL-7702 cytotoxicity than the mitoxantrone. Promisingly, the most active compound, 6a, was successfully used in living SH-SY5Y cell imaging and had predictable lipophilicity and blood-brain-barrier permeation properties. These hybrids should undergo further systematic study in the treatment of Alzheimer's disease.
研究领域:
药理学
·
神经科学
·
药物化学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Chenglong Lv,Xinyi Pang,Jing Sun,Xiangfei Li,Yingjian Lu
Hypercholesterolemia is a great threat to humans. Bile salt hydrolase (BSH)-producing lactic acid bacteria (LAB) may alleviate it, but current screening methods are inadequate. This study aimed to establish a more comprehensive in vitro method to screen BSH-producing LAB with greater potential for anti-hypercholesterolemia. Forty-one LAB were initially isolated from infant feces and 37 strains could produce BSH. Strains with BSH over 2 U/mg for sodium glycodeoxycholate and sodium taurodeoxycholate were used to analyse cholesterol degradation rate, hydrophobicity, self-aggregation, gastric fluid tolerance, and intestinal fluid tolerance. Based on the results of these indicators, Lactococcus lactis Y17, L. rhamnosus Q2, and L . fermentum Q11 with the top scores were considered anti-hypercholesterolemia candidates using a principal component analysis evaluation. Antioxidant and Caco-2 adhesion assays showed that these three strains exhibited excellent antioxidant ability and Caco-2 adhesion ability. Their total antioxidant capacity was above 0.99 μmol/L, while the Caco-2 adhesion rate was higher than 8.22%. Safety assessments, via antibiotic susceptibility and hemolysis tests, confirmed their safety. In the HepG2 cells assay, the total cholesterol content of the Y17, Q2, and Q11 groups was reduced by 0.525 mmol/L, 0.426 mmol/L, and 0.581 mmol/L, which verified the potential of the three LAB in anti-hypercholesterolemia. In addition, they could enhance cholesterol uptake and bile acid synthesis in HepG2 cells by upregulating the mRNA expression of bile acid synthase ( CYP7A1 and CYP8B1 ) and cholesterol uptake receptors ( NPC1L1 and LDLR ). The results showed that the three LAB could be developed into anti-hypercholesterolemia foods with beneficial properties.
研究领域:
微生物学
·
营养学
·
生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yazhou Xu,Tao Xiong,Linli zhang,Tonghao Du,Philippe Madjirebaye,Mingwei Zhao,Xinyi Kang
Hyperglycemia and diabetes are widely recognized as prevalent metabolic disorders, often associated with various complications, including hepatic and renal dysfunction as well as cardiovascular damage. Lactic acid bacteria (LAB) strains have been proposed as potential agents for ameliorating hyperglycemia without causing adverse effects. In this study, we established a multi-target, comprehensive in vitro methodology to screen LAB strains with enhanced potential against hyperglycemia, using Lactobacillus rhamnosus (LGG) as a reference strain. We initially selected 43 strains isolated from the human gastrointestinal tract based on their α-glucosidase inhibitory activity; subsequently, their capacity to inhibit α-amylase was evaluated through α-amylase inhibition assays. Furthermore, insulin sensitization was assessed via tyrosine phosphatase 1B inhibition, along with antioxidant capabilities. To thoroughly evaluate the efficacy of LAB strains in improving abnormal glucose metabolism, we developed an insulin-resistant HepG2 cell model. Principal component analysis revealed that NCUH012072 ( Lacticaseibacillus paracasei ), NCUH003081 ( Limosilactobacillus fermentum ), NCUH064006 ( Limosilactobacillus reuteri ), and two strains of NCUH001099 ( Lactiplantibacillus plantarum ) exhibited superior hypoglycemic properties. Concurrently, these LAB strains demonstrated robust acid resistance and bile salt tolerance while showing neither hemolytic activity nor antibiotic resistance. These findings suggested that NCUH012072 ( Lacticaseibacillus paracasei ), NCUH003081 ( Limosilactobacillus fermentum ), and NCUH064006 ( Limosilactobacillus reuteri ) are promising probiotic candidates for glycemic control.
研究领域:
微生物学
·
营养科学
·
药理学
·
代谢紊乱
·
益生菌
✓ 已验证
DOI
高影响因子
Research
·
2023
·
IF 11
Guangchun Song,Jia Xu,Hong Zhong,Qi Zhang,Xin Wang,Yitong Lin,Scott P. Beckman,Yunbo Luo,Xiaoyun He,Jin-Cheng Li,Kunlun Huang,Nan Cheng
The enzyme-mimicking catalytic activity of single-atom nanozymes has been widely used in tumor treatment. However, research on alleviating metabolic diseases, such as hyperglycemia, has not been reported. Herein, we found that the single-atom Ce-N4-C-(OH)2 (SACe-N4-C-(OH)2) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N4-C-(OH)2 nanozyme initiated a cascade reaction involving superoxide dismutase-, oxidase-, catalase-, and peroxidase-like activity to overcome the limitations associated with the substrate and produce •OH, thus improving glucose intolerance and insulin resistance by increasing the phosphorylation of protein kinase B and glycogen synthase kinase 3β, and the expression of glycogen synthase, promoting glycogen synthesis to improve glucose intolerance and insulin resistance in high-fat diet-induced hyperglycemic mice. Altogether, these results demonstrated that the novel nanozyme SACe-N4-C-(OH)2 alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.
研究领域:
纳米技术
·
生物化学
·
代谢疾病
·
药理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）