TOXICOLOGY IN VITRO
·
2023
·
IF 3.2
Weiyi Ye,Zhen Wang,Xin Lv,Hang Yin,Lili Jiang,Zhe Wang,Yong Liu
Ponatinib is an efficient oral tyrosine kinase inhibitor (TKI) for T315I-positive Ph + ALL and T315I-positive chronic myeloid leukemia (CML) or BCR-ABL when no other TKIs can be prescribed. In this research, we evaluated the inhibitory effects of ponatinib on human recombinant UDP-glucuronosyltransferases (UGTs) and predicted the magnitude of potential drug-drug interaction (DDI) risk of co-treatment with ponatinib and UGTs substrates by using in vitro-in vivo extrapolation (IVIVE) method. Our study presented that ponatinib showed a broad-spectrum inhibition against UGTs. Particularly, ponatinib exhibited potent inhibitory effects towards UGT1A7, UGT1A1, and UGT1A9 with IC 50 values of 0.37, 0.41, and 0.89 μM, respectively, which might lead to clinically significant DDI.
研究领域:
药理学
·
临床医学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2013
·Vol. 5
·期 21
·6106-6113
·
IF 1.855
Yajing Lei,Lizheng Fang,Muhammad Sajid Hamid Akash,Zhiming Liu,Weixing Shi,Shuqing Chen
Bisphenol A (BPA) is widely used to manufacture polycarbonate plastics and epoxy resins, which are in widespread use in China. Concerns about potential health impacts from exposure to BPA among the general population are increasing day by day. A sensitive and specific antibody was prepared to develop and compare direct and indirect competitive enzyme-linked immunosorbent assays (ELISAs) for the determination of BPA in human urine. The IC50 value and limit of detection (LOD) for the direct competitive ELISA were 5.5 ng mL−1 and 0.03 ng mL−1 respectively whereas, for the indirect competitive ELISA, the IC50 value and LOD were 7.0 ng mL−1and 0.08 ng mL−1, respectively. We found that the direct competitive ELISA was more specific and sensitive than the indirect competitive ELISA. The established immunoassays were also applied in the determination of BPA in human urine samples. The results from fortified samples and real samples indicated that the direct competitive ELISA was more sensitive and reliable for the measurement of BPA in human urine as compared to the indirect competitive ELISA.
研究领域:
环境健康
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分析化学
·
毒理学
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产品关联
DOI
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2024
·
IF 5.6
Yanju Lu,Fengqi Chen,Yuxiang Chen,Jing Wang,Shenlin Huang
Isopimaric acid is derived from a natural resource of pine resin, which is inherently biologically active. A series of seven novel isopimaric heterocyclic sulfonamides derivatives were synthesized using isopimaric acid as the lead compound to splice with the sulfonamides by chlorinated and amidated to screen out compounds with anti-tumor activity. And it was characterized using infrared spectrum (IR), nuclear magnetic resonance (NMR), and mass spectrometry. All of the compounds were screened for their antitumor activity against cervical cancer cells (Hela), breast cancer cells (MDA-MB-231), prostate cancer cells (PC-3), and hepatoma cells (HepG-2). Some of the test compounds showed potent antitumor activity. Among the isopimaric heterocyclic sulfonamides derivatives synthesized, compound 5a inhibited the growth of the four tumor cells mentioned above with IC 50 values in the range of 28.53–40.98 µM. In addition, compound 5c exhibits inhibitory activity toward these tumor cells with IC 50 values in the range of 56.27–60.62 µM. In conclusion, isopimaric heterocyclic sulfonamides derivatives may provide a basis for further research on anti-tumor drugs.
研究领域:
药物化学
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肿瘤学
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有机合成
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产品关联
DOI
高影响因子
RSC Advances
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2018
·Vol. 8
·期 72
·41377-41388
·
IF 2.936
Xiao-Qian Chi,Cheng-Ting Zi,Hong-Mei Li,Liu Yang,Yong-Feng Lv,Jin-Yu Li,Bo Hou,Fu-Cai Ren,Jiang-Miao Hu,Jun Zhou
In order to better understand the structure–activity relationship of mangostin, a series of xanthone derivatives based on α-mangostin were designed and synthesized. All the compounds were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using MTT assays. Most of them showed cytotoxicity and most of all, compounds 1a and 2h showed the highest cytotoxic potency by HL-60 cancer cell lines with IC50 values of 5.96 μM and 6.90 μM respectively; compound 3e showed the highest cytotoxic potency against SMMC-7221 cancer cell line with IC50 values of 3.98 μM; compounds 2e and 2m showed lower cytotoxicity but higher selectivity than α-mangostin against HL-60 and SMMC-7221 cancer cell lines respectively. Structure–activity relationship analysis indicates that the maintenance of the isopentene group at C-8 is essential for the cytotoxic activity.
研究领域:
药物化学
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肿瘤学
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有机合成
✓ 已验证
DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
·
2022
·Vol. 58
·期 10
·1520-1526
·
IF 0.862
Yang Shun,Zou Jing-Pei,Li Xiang-Rong,Li Rui,Qian Jing-Jing,Wu Wen-Long,Su Jia-Bin,Chen Ke-Qi,Qin Tian,Liu Shan-Ming,Liu Wei-Wei,Shi Da-Hua
Abstract A series of 1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated as acetylcholinesterase inhibitors. Their structure was confirmed by IR, NMR, and high-resolution mass spectra. The synthesized compounds showed significant acetylcholinesterase inhibitory activity with an IC 50 value of 0.07 μM for the most potent compound. Molecular docking study of the most active compound indicated that it interacted with the crucial amino acids present at the catalytic active site and peripheral anionic site of acetylcholinesterase. The results suggested that the obtained 1,3,4-oxadiazole derivatives may be the potential drug candidates for the treatment of Alzheimer’s disease as AChE inhibitors.
研究领域:
药物化学
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神经科学
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有机合成
✓ 已验证
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2014
·
IF 6.451
Huanshun Yin,Xinxu Wang,Yunlong Guo,Yunlei Zhou,Shiyun Ai
An effective assay method for monitoring protein kinase activity and screening inhibitors is greatly beneficial to kinase-related drug discovery, early diagnosis of diseases, and therapeutic effect evaluation. Herein, we develop a simple electrochemical method for detecting the activity of casein kinase II (CK2) based on phosphorylation against carboxypeptidase Y (CPY) digestion triggered signal amplification , where CK2 catalyzed phosphorylation event protects the substrate peptide from the digestion of CPY, maintains the repulsive force of the substrate peptide towards the redox probe, and results in a weak electrochemical signal. Whereas, without phosphorylation, the substrate peptide is digested by CPY and a strong electrochemical signal is obtained. The detection feasibility is demonstrated for the assay of CK2 activity with low detection limit of 0.047 unit/mL. Moreover, the biosensor was used for the analysis of kinase inhibition. Based on the electrochemical signal dependent inhibitor concentration, the IC 50 value of ellagic acid was estimated to be 39.77 nM. The proposed method is also successfully applied to analyze CK2 activity in cell lysates, proving the applicability in complex biological samples.
研究领域:
生物化学
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分析化学
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药物发现
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疾病诊断
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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
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化学
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微生物学
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产品关联
DOI
PubMed
高影响因子
ChemistryOpen
·
2024
·
IF 2.5
Yuanyong Yao,Tao Wu,Meng Zhang,Daihua Fu,Hai Yang,Shixue Chen
Graphical The test method for assaying inhibitory effects of bioflavonoids on xanhine oxidase in vitro has been improved successfully with the equipment of UV-Vis technique. In the improved test method, there is a micro-environment surrounding XOD has been created in the presence of •O 2 - , which is similar to that of in vivo . Simultaneously, the inhibition of dihydromyricetin as a chiral flavonoid was effectively assayed by the improved test method, indicating dihydromyricetin enabling to be a potent inhibitor of XOD, resulting from the selective transformation of DMY to MY occurred. The difference on inhibitory effects of bioflavonoids inhibiting XOD activity assayed by varying test methods cause of us to be further in consideration. The reported test method creating a micro-environment surrounding XOD in the absence of ⋅O 2 − , which is seemly different from the assay in vivo . So, the vitro test method for assaying XOD activity is necessary to be improved for selection of potential inhibitors in the presence of ⋅O 2 − . The inhibitory results demonstrated that bioflavonoids of MY, DMY, QUE and LUT are capable to be on effective IC 50 values, but others are not. As well, their resulting inhibitions determined by the improved test method are much less than that reported in the literature, indicating that their chemical affinities with XOD become weaker. Moreover, DMY assayed on the inhibitions of XOD in the improved test method performs to be a better inhibitor, as compared to the assay of the reported test methods. Abasing on the transformation of DMY into MY in the presence of ⋅O 2 − , the good inhibition of DMY on XOD activity can be explained by the synergistic effect of MY.
研究领域:
生物化学
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药理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Mengting Wang,Jinyuan Shi,Lei Wang,Yaqin Hu,Xingqian Ye,Donghong Liu,Jianchu Chen
In this study, lotus leaf flavonoids (LLF) were found to show a notable inhibition activity on α-amylase in a mixed-type manner with IC 50 value of (5.58 ± 0.10) mg/mL. The intrinsic fluorescence of α-amylase was quenched by the interaction with LLF through a static quenching mechanism, and LLF-α-amylase complex was spontaneously formed mainly driven by the hydrophobic interaction and hydrogen bonding. Multispectroscopic analyses (synchronous fluorescence, three-dimensional fluorescence, circular dichroism (CD) and fourier transform infrared spectra (FT-IR)) comprehensively demonstrated that the binding of LLF to α-amylase would change the conformation and microenvironment of α-amylase, resulting in inhibiting the enzyme activity. The present study indicated that LLF had potential to be as an ingredient in functional food for the prevention of type-2 diabetes.
研究领域:
生物化学
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药理学
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食品科学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Jinpeng Liu,Mashooq Khan,Yong Wei,Anna Liu,Tao Wang,Qiongzheng Hu,Li Yu
High-throughput screening of lipase inhibitors is critical for developing anti-obesity drugs. Herein, a robust and versatile sensing platform based on the difference in the sliding time of droplets on liquid crystal-infused porous surfaces (LCIPS) is developed to detect lipase inhibitors. Lipase catalyzes glycerol trioleate (GT) to produce oleate that can adsorb at the solution/liquid crystal (LC) interface due to its high amphiphilicity, which impedes the sliding of droplets on LCIPS, resulting in an extended sliding time. However, in the presence of lipase inhibitors, the enzymatic hydrolysis of GT by lipase is inhibited, which shortens the sliding time. The screening of three lipase inhibitors, orlistat, cetilistat, and epigallocatechin gallate (EGCG), popular anti-obesity drugs, is demonstrated to have IC 50 values of 17.45 ± 3.15 nM, 72.15 ± 6.32 nM, and 2.19 ± 0.24 μM, respectively. This study provides a simple, inexpensive, portable, user-friendly, and instrument-free method for rapid, accurate, and high-throughput screening of lipase inhibitors. The LCIPS-based sensing platform is up-and-coming in developing advanced bioanalytical sensors.
研究领域:
药学
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生物技术
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Biomed Research International
·
2013
·
IF 0
Li Lv,Yuanyuan Shen,Min Li,Xiaofen Xu,Mingna Li,Shengrong Guo,Shengtang Huang
A novel 4-arm poly(ethylene glycol)-block-poly(anhydride-esters) amphiphilic copolymer (4-arm PEG-b-PAE) was synthesized by esterization of 4-arm poly(ethylene glycol) and poly(anhydride-esters) which was obtained by melt polycondensation of α-, ω-acetic anhydride terminated poly(L-lactic acid). The obtained 4-arm PEG-b-PAE was characterized by 1H-NMR and gel permeation chromatography. The critical micelle concentration of 4-arm PEG-b-PAE was 2.38 μg/mL. The curcumin-loaded 4-arm PEG-b-PAE micelles were prepared by a solid dispersion method and the drug loading content and encapsulation efficiency of the micelles were 7.0% and 85.2%, respectively. The curcumin-loaded micelles were spherical with a hydrodynamic diameter of 151.9 nm. Curcumin was encapsulated within 4-arm PEG-b-PAE micelles amorphously and released from the micelles, faster in pH 5.0 than pH 7.4, presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. The hemolysis rate of the curcumin-loaded 4-arm PEG-b-PAE micelles was 3.18%, which was below 5%. The IC50 value of the curcumin-loaded micelles against Hela cells was 10.21 μg/mL, lower than the one of free curcumin (25.90 μg/mL). The cellular uptake of the curcumin-loaded micelles in Hela cell increased in a time-dependent manner. The curcumin-loaded micelles could induce G2/M phase cell cycle arrest and apoptosis of Hela cells.
研究领域:
药学
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材料科学
·
纳米技术
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
JOURNAL OF FOOD BIOCHEMISTRY
·
2019
·Vol. 43
·期 11
·e13028
·
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
·
肿瘤学
·
食品科学
·
植物科学
✓ 已验证
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）