Journal of Applied Spectroscopy
·
2022
·Vol. 89
·期 3
·559-566
·
IF 0.816
Gao Ch.,Du H.
Forsythoside E is one of the major secondary metabolites in Forsythia suspensa . The interactions between forsythoside E and two types of cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated in PBS buffer (pH 7.40) by using multispectroscopic techniques. Forsythoside E increased the fluorescence intensity of AChE but quenched the fluorescence of BChE. Synchronous fluorescence studies showed that forsythoside E mainly acts on tyrosine residues of AChE and tryptophan residues of BChE. It was also proved that the complex between the compound and cholinesterases formed spontaneously at a stoichiometric ratio of 1:1 via multispectral technology. Finally, forsythoside E inhibited the activities of cholinesterases with similar IC 50 values of 1.08 mM for AChE and 0.92 mM for BChE. The results illuminate the details of the interaction between forsythoside E and cholinesterases.
研究领域:
药理学
·
生物化学
·
分子生物学
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DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 8
·e202300942
·
IF 2.9
Jiayi Ou,Weiyun Tan,Gong Chen,Xianjing Yang,Yan Luo,Xiaobao Jin,Lianbao Ye
Glioma is the most common brain tumor and its treatment options are limited. Abietic acid and dehydroabietic acid are tricyclic diterpenoid oxygen compounds with strong lip solubility and anti-glioma activity. In this study, novel rosin diterpenoid derivatives were designed and synthesized using abietic acid and dehydrogenated abietic acid as lead compounds and their activities against T98G, U87MG, and U251 cells were evaluated by CCK-8 methods. The in vivo activity of compounds with stronger activity in vitro was preliminarily studied through the Zebrafish model. The results showed that the IC 50 values of B6 , B8 , B10 , and B12 were 11.47 to 210.6 μM, which were exhibited higher antiproliferative potency against T98G, U87MG, and U251. The scratch experiment showed that B12 inhibited the migration of T98G in a time-dependent and concentration-dependent manner. The results of in vivo activity further explained that B12 could inhibit the proliferation of the T98G. The pKa values of B6 , B8 , B10 , and B12 were 7.17 to 7.35, which were within the ideal range of glioma drugs. The ADME predictions indicated that these derivatives could pass through the blood-brain barrier. In addition, molecular docking primarily explained interaction between compounds and protein. These results suggested that B12 should be a promising candidate that merits further attention in the development of anti-glioma drugs. Graphical
研究领域:
药理学
·
肿瘤学
·
药物化学
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Peng Zhu,You Yang,Jianqiang Qian,Jun Han,Dairui Kong,Bo Sun,Jian Zhang,Jingtao Wei,Qulian Guo,Sihui Nian,Lixiang Zhou,Guodong Wang,Shaohua Hou
Mitogen-activated protein kinase–interacting kinases (MNKs) play a key role in the occurrence and migration of tumors and have become promising targets for tumor therapy. Nevertheless, the development progress on the MNKs inhibitors against cancer was relatively slow. In this study, compound 4s (MNK1/2 half-maximal inhibitory concentration [IC 50 ] = 987/1048 nM), a promising MNKs inhibitor was discovered based on virtual screening. After the structural optimization of compound 4s , 18 novel thiophene [2,3-D] pyrimidine–thiazole derivatives were designed and prepared, and their inhibitory effect on MNKs was determined. Among which, compound 5l exhibited the best inhibitory activity on MNKs (MNK1/2 IC 50 = 23/62 nM) and relatively high selectivity among 125 kinases. Results from in vitro experiments indicated that compound 5l could significantly inhibit the in vitro proliferation (IC 50 = 0.8 ± 0.1 μM) and migration of breast cancer cells, which demonstrated that compound 5l is a promising MNK inhibitor to treat breast cancer and need further study.
研究领域:
药理学
·
肿瘤学
·
药物化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Lingling Wang,Xiuhua Zhao,Fengjian Yang,Weiwei Wu,Mingfang Wu,Yuanyuan Li,Xiaoxue Zhang
In this work, paclitaxel was loaded into porous starch in the form of nanoparticles (PNPS), and the properties of PNPS were investigated by using raw paclitaxel and the system of paclitaxel directly loaded into porous starch (PPS) as control groups. According to the tested results, the drug loading ( DL ) and encapsulation efficiency ( EE ) of PNPS were 14.13% ± 0.27% and 73.92% ± 0.54%, higher than that of PPS (9.79% ± 0.31% and 71.17% ± 0.67%) respectively. Compared with raw paclitaxel and PPS, PNPS exhibited the more prominent dissolution rate and bioavailability, in which the bioavailability of PPS and PNPS were 2.94 and 5.42 times of that of raw paclitaxel respectively. In addition, the IC 50 values of raw paclitaxel, PPS and PNPS on Lewis Lung Carcinoma (LLC) cells were 17,703.41 ± 15.76 μM, 95.10 ± 5.32 μM and 85.68 ± 7.38 μM respectively. Furthermore, the residues of acetone in PPS and PNPS were less than the ICH limit for acetone in class III solvents. To summarize, the preparation of PNPS was a potential method to improve the dissolution and bioavailability of paclitaxel.
研究领域:
药学
·
药物递送系统
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Jia Cheng Qian,Heng Peng Zhang,Yi Wang,Dan Liu
Cruciferous vegetables (CVs) are globally consumed with some health benefits believed to arise from indole-3-carbinol (I3C), a labile phytochemical liberated from indole glucosinolates, but few reports describe the effect of cooking on I3C reactions. Here, we present heat-promoted direct conversions of I3C in broccoli florets into indole derivatives, which are unique in the N -indolylmethylation and -hydroxymethylation of indole nuclei by 3-methyleneindole and formaldehyde formed in situ from the I3C dehydration and the dimerization of I3C to 3,3′-diindolylmethane (DIM), respectively. Such N -substituted indoles were found in a range of 0.4–4.6 μg per gram of steamed broccoli florets, with a novel compound N -(indol-3-ylmethyl)-3,3′-diindolylmethane (DIM-1) bio-evaluated to inhibit A375 cells with an IC 50 value of 1.87 μM. In aggregation, the investigation discloses the promoting effect of heating on the I3C transformation in CVs and identifies DIM-1 as an anti-cancer drug candidate, and thus updates the knowledge of I3C and bioactive derivatives thereof.
研究领域:
生物化学
·
药理学
·
癌症研究
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2019
·
IF 4.027
Yu-Heng Hu,Jie Yang,Yun Zhang,Ke-Chun Liu,Teng Liu,Jie Sun,Xiao-Jing Wang
The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
研究领域:
药理学
·
神经科学
·
药物设计
✓ 已验证
DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2022
·
IF 2.488
Xin Liu,Zhihong Cheng
Euphorbia factor L1 (EFL1, 1) is a natural tri-ester of 6,17-epoxylathyrol with cancer multidrug resistance (MDR) reversal activity. Several EFL1 derivatives (2–9) were prepared by chemical and microbial transformations and their ability to inhibit P-glycoprotein (P-gp) activity was estimated. Six de-acylated derivatives (2–7) were obtained through base-hydrolysis of 1, and the base-catalysed hydrolysis via KOH and NaOH yielded different hydrolysed products of 1. Two biotransformed products (8–9) were directly obtained via microbial transformation of 1, and 8 was also formed by microbial conversion of the hydrolysed product 3. The P-gp modulation of 1–9 was assessed by a zebrafish model. The substrate 1 and its biotransformed product 9 as the tri-esters of lathyranes possessed the highest P-gp inhibitory activity with IC50 values of 34.97 and 15.50 µM, respectively, through down-regulating P-gp expression at the protein level rather than at MDR1 mRNA level.
研究领域:
药理学
·
生物化学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Ting Zhou,Guangzhao He,Changjia Hu,Kang Wu,Ying Liu,Jianguo Li,Anping Deng
5-Fluorouracil (5-FU) is an effective anticancer drug widely used in cancer treatment. In this study, two 5-FU derivatives containing a spacer arm with the carboxylic group at the end were synthesized, which were linked to the carrier proteins to form 5-FU-protein conjugates used as the immunogens for the production of monoclonal antibody (mAb). Based on the produced mAb, the highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for 5-FU detection was established. The IC 50 and LOD values of the assay were found to be 19.5 ng mL −1 and 0.5 ng mL −1 , respectively. There was no cross-reactivity (CR) of the ELISA with cytosine , thymine and uracil , which avoided the interference from inherent pyrimidines. The CR values of the assay with three substitutes of 5-FU (tegafur, 5-fluoro-2′-deoxyuridine, carmofur) were within 9.7%–17.6%. The produced mAb was also applied in sample extraction. The immuno-affinity column capable specific capturing 5-FU was prepared by immobilizing the mAb on Sepharose-4B gel and filling into a SPE column. The recoveries of 5-FU in spiked samples measured by ELISA were 72.4%–90.7% with RSD of 3.6%–8.3%. Five blood samples collected from patients were extracted by immuno-affinity column, then measured by ELISA and confirmed by HPLC-MS/MS. There was a good correlation between HPLC-MS/MS and ELISA. It is demonstrated that the developed ELISA combined with immuno-affinity extraction can be a powerful alternative method for the detection of 5-FU in blood samples.
研究领域:
药理学
·
分析化学
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免疫学
·
临床化学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 9
·e76007
·
IF 3.73
Xiang Li,Yuanyuan Liu,Xueling Hou,Hongjun Peng,Li Zhang,Qingbo Jiang,Mei Shi,Yun Ji,Yuyue Wang,Weifeng Shi
Enterovirus 71 (EV71) is an etiology for a number of diseases in humans. Traditional Chinese herbs have been reported to be effective for treating EV71 infection. However, there is no report about the antiviral effects of CHA against EV71. In this study, plaque reduction assay demonstrated that the inhibitory concentration 50% (IC50) of CHA on EV71 replication is 6.3 µg/ml. When both CHA (20 µg/ml) and EV71 were added, or added post-infection at different time points, CHA was able to effectively inhibit EV71 replication between 0 and 10 h. In addition, CHA inhibited EV71 2A transcription and translation in EV71-infected RD cells, but did not affect VP1, 3C, and 3D expression. Furthermore, CHA inhibited secretions of IL-6, TNF-α, IFN-γ and MCP-1 in EV71-infected RD cells. Altogether, these results revealed that CHA may have antiviral properties for treating EV71 infection.
研究领域:
病毒学
·
药理学
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2024
·
IF 1.3
Lin Liang,Xi Yuan,Xiao-Ya Xian,Xian-Li Zhou,Tong-Dong Kuang,Jin-Tao Gao,Li-Sheng Wang,Cheng-Qin Liang
Two new quinazolinone alkaloids, benzomalvin F (1), and quinadoline C (2), along with four known quinazolinones (3-6), were isolated from cultures of the wetland-soil-derived fungus Aspergillus udagawae from the Huixian wetland in Guilin. Their structures were elucidated based on detailed spectroscopic analysis, including 1D, 2D NMR, mass spectrometry, and IR spectra. In addition, the anti-inflammatory results showed that compounds 1, 2, 4, and 5 had significant inhibitory effects on NO production in RAW264.7 cells activated by lipopolysaccharide (LPS), with IC50 values of 24.5 ± 0.1, 29.7 ± 0.1, 29.4 ± 0.1, and 31.0 ± 0.1 µM respectively, compared with the positive control indomethacin (IC50 = 31.6 ± 0.4 μM).
研究领域:
药理学
·
化学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Quality and Safety
·
2021
·
IF 3.102
Xie Jiahong,Cui Haoxin,Xu Yang,Xie Lianghua,Chen Wei
ObjectivesThis study was conducted to investigate the xanthine oxidase (XO) inhibitory activities of 18 monomeric anthocyanins from berry fruits and roselle, and to illustrate the underlying mechanism of the most active anthocyanin delphinidin-3-O-sambubioside.Materials and MethodsEighteen monomeric anthocyanins were prepared and purified in our laboratory. The inhibitory properties of anthocyanins were investigated by in vitro inhibitory activity studies and fluorescence quenching studies; the inhibitory mechanism was explored through kinetic studies, fluorescence quenching studies, circular dichroism analysis and computational docking simulations.ResultsXO inhibitory activities of anthocyanins were related to the structures of B rings and glycosides. Among all the tested anthocyanins, delphinidin-3-O-sambubioside showed the most potent inhibitory activity with an IC50 of 17.1 μM, which was comparable to the positive control allopurinol. Spectroscopic results revealed that delphinidin-3-O-sambubioside could spontaneously interact with XO and induce conformational changes. Computational docking study indicated that delphinidin-3-O-sambubioside could bind to XO with a proper orientation, stably formed π–π interactions and hydrogen bonds with key residues, thus preventing the substrate from entering the active pocket.ConclusionsIn brief, our study identified delphinidin-3-O-sambubioside as a potent XO inhibitor from natural anthocyanins, which is potentially applicable for prevention and treatment of hyperuricemia.
研究领域:
药理学
·
生物化学
·
天然产物化学
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产品关联
DOI
高影响因子
Polymer Chemistry
·
2019
·Vol. 10
·期 39
·5353-5363
·
IF 4.76
Jiaxu Li,Liuchun Zheng,Haihua Xiao,Chuncheng Li,Shaohua Wu,Yaonan Xiao,Jiajian Liu,Bo Zhang
Zwitterions of L-cysteine have been applied to modify polyester, and the obtained zwitterionic polyester is employed to load a platinum(IV) drug to prolong the circulation time of the drug in blood and improve the stability of drug loading due to the good biocompatibility and antifouling properties. When used as multifunctional drug delivery vehicles, the nanoparticles not only exhibit a pH- and reduction-responsive drug release character, but also possess high ovarian cancer treatment efficiency in vitro. As compared to cisplatin, the IC50 value of the platinum(IV) drug loaded nanoparticles decreased by 57.44%, demonstrating that the platinum(IV) drug loaded nanoparticles exhibit strong toxicity to A2780 cells. In particular, in this study, aliphatic amine highly selective dye 5(6)-carboxyfluorescein N-succinimidyl ester is first used to label the drug-loaded zwitterionic nanoparticles, aiming to trace the location of the nanoparticles in cancer cells. All these results demonstrate potential applications of this type of zwitterionic nanostructure in biomedical fields.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
纳米技术
✓ 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）