LANGMUIR
·
2025
·
IF 3.9
Jiajun Li,Sihui Wu,Xueran Shi,Yingbo Cao,Han Hao,Jing Wang,Qian Han
Warfarin (WAR), an effective oral anticoagulant, is of utmost importance in treating many diseases. Despite its significance, rapid and precise discrimination of WAR remains a formidable challenge, especially facing its structural analogs of metabolites. Here, three kinds of herb-derived N-doped carbon dots (NCDs) were greenly synthesized via a fast and simple microwave-assisted method. Three NCDs showcased respectable blue fluorescent (FL) properties and sensing capabilities for the discrimination of WAR and its metabolites. To improve accuracy in identifying WAR and its metabolites, a sensor array composed of three unique herb-derived NCDs was meticulously designed. Combined with the machine learning model, the sensor array displayed a strong immunity to interference in the discrimination of the WAR, even in unknown samples. Meanwhile, the FL sensing mechanism is deeply expounded. The methodology proffers broad prospects for biomass-derived nanomaterials and provides an effective and feasible project for pharmaceutical analysis by capitalizing on machine learning.
研究领域:
药学
·
材料科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 8
·1791
·
IF 4.6
Jiawei Li,Cong Zhang,Xiaohui Wang,Jinjing Zhang,Hanwen Liu,Xu Wu
Pharmaceutical quality control plays a critical role in safeguarding patient safety and ensuring therapeutic efficacy. However, conventional analytical methods are often hindered by laborious procedures and complex chemical preparation requirements. This study presents a rapid, non-destructive pharmaceutical analysis approach by introducing terahertz spectroscopy for the dual-parametric detection of the anticoagulant warfarin. Characteristic absorption peaks of warfarin within the 4–10 THz range were experimentally identified and theoretically resolved through density functional theory calculations, employing both single-molecule and unit cell models. Furthermore, three strong absorption peaks were selected to construct multivariate regression models correlating spectral parameters (peak intensity and area) with warfarin weight, achieving a detection limit of 0.641 mg within a 5 min analytical workflow. This approach enables simultaneous molecular fingerprint identification and quantitative determination without chemical modification, meeting the requirements for the rapid screening of active pharmaceutical ingredients.
研究领域:
药学
·
光谱学
·
计算化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2017
·
IF 2.536
Yusheng Yuan,Liu Yang,Shaopu Liu,Jidong Yang,Hui Zhang,Jingjing Yan,Xiaoli Hu
A sensitive fluorescence sensor for warfarin was proposed via quenching the fluorescence of l -tryptophan due to the interaction between warfarin and l -tryptophan. Warfarin, as one of the most effective anticoagulants , was designed and synthesized via lipase from porcine pancreas (PPL) as a biocatalyst to catalyze the Michael addition of 4-hydroxycoumarin to α, β-unsaturated enones in organic medium in the presence of water. Furthermore, the spectrofluorometry was used to detect the concentration of warfarin with a linear range and detection limit (3σ/k) of 0.04–12.0 μmol L − 1 (R 2 = 0.994) and 0.01 μmol L − 1 , respectively. Herein, this was the first application of bio-catalytic synthesis and fluorescence for the determination of warfarin. The proposed method was applied to determine warfarin of the drug in tablets with satisfactory results.
研究领域:
药物化学
·
分析化学
·
生物催化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2019
·
IF 1.902
Huanying Ye,Danjuan Sui,Wei Liu,Yuannan Yuan,Zhen Ouyang,Yuan Wei
1. CYP2C11 is the most abundant isoform of cytochrome P450s (CYPs) in male rats and is considered the main enzyme for warfarin metabolism.2. To further access the in vivo function of CYP2C11 in warfarin metabolism and efficacy, a CYP2C11-null rat model was used to study warfarin metabolism with both in vitro and in vivo approaches. Prothrombin time (PT) of warfarin was also determined.3. The maximum rate of metabolism (Vmax) and intrinsic clearance (CLint) of liver microsomes from CYP2C11-null males were reduced by 37 and 64%, respectively, compared to those in Sprague Dawley (S-D) rats. The Km of liver microsomes from CYP2C11-null males was increased by 73% compared to that of S-D rats. The time to reach the maximum plasma concentration (Tmax) of warfarin in CYP2C11-null males was significantly delayed compared to that in S-D males, and the CL rate was also reduced. The PT of CYP2C11-null rats was moderately longer than that of S-D rats.4. In conclusion, the clearance rate of warfarin was mildly decreased and its anticoagulant effect was moderately increased in male rats following CYP2C11 gene knockout. CYP2C11 played a certain role in the clearance and efficacy of warfarin, while it did not seem to be essential.
研究领域:
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
·
2012
·Vol. 87
·期 12
·1709-1714
·
IF 2.168
Bang-Hua Xie,Zhi Guan,Yan-Hong He
BACKGROUND: Biocatalytic promiscuity has attracted much attention from chemists and biochemists in recent years. Warfarin, one of the most effective anticoagulants, has been introduced for clinical use as a racemate for more than half a century. Although some different chemical strategies towards the synthesis of optically active warfarin have been reported, biocatalytic preparation of warfarin remains unexploited. RESULTS: Lipase from porcine pancreas (PPL) was used as a biocatalyst to catalyze the Michael addition of 4-hydroxycoumarin to α,β-unsaturated enones in organic medium in the presence of water to synthesize warfarin and derivatives. The products were obtained in moderate to high yields (up to 95%) with none or low enantioselectivities (up to 28% ee). The influence of reaction conditions including solvents, temperature and molar ratio of substrates was systematically investigated. CONCLUSION: Among the many reported lipase-catalyzed Michael additions, only a few showed enantioselectivity. Therefore, this Michael addition activity of, for example, PPL is a valuable case of enantioselective lipase catalytic promiscuity. In addition, it was the first time warfarin and derivatives were prepared using a biocatalyst. Copyright © 2012 Society of Chemical Industry
研究领域:
生物化学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 9
·2154
·
IF 3.098
Yunchang Fan,Dongxu Cai,Xin Wang,Lei Yang
Recently, ionic liquids (ILs) have been regarded as ideal media for non-aqueous bio-catalysis. In this work, the synthesis of warfarin by the lipase-catalyzed Michael addition in IL media and the parameters that affected the warfarin yield were investigated. Experimental results demonstrated that the chemical structures of the ILs were a major factor for influencing the warfarin yield. The ILs containing the NTf2–anion were suitable reaction media due to the high chemical stability of this anion. The incorporation of the hydroxyl group on the IL cation significantly improved the lipase activity due to the H2O-mimicking property of this group. The lipase activity decreased by increasing the alkyl chain length on the IL cation due to the non-polar domain formation of the IL cation at the active site entrance of lipase. The ILs and lipase could be reused no less than five times without reduction in the warfarin yield.Keywords:ionic liquids (ILs);lipase;Michael addition;warfarin;bio-catalysis
研究领域:
生物化学
·
制药工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2016
·
IF 2.641
Hua Sun,Tianpeng Zhang,Zhufeng Wu,Baojian Wu
ABSTRACT: In this study, we aimed to determine the modulatory effects of warfarin (an extensively used anticoagulant drug) and its metabolites on UDP-glucuronosyltransferase (UGT) activity and to assess the potential of warfarin to alter the pharmacokinetics of zidovudine (AZT). The effects of warfarin and its metabolites on glucuronidation were determined using human and rat liver microsomes (HLM and RLM) as well as expressed UGTs. The mechanisms of warfarin–UGT interactions were explored through kinetic characterization and modeling. Pharmacokinetic studies with rats were performed to evaluate the potential of warfarin to alter the pharmacokinetics of AZT. We found that warfarin was an effective modifier of a panel of UGT enzymes. The effects of warfarin on glucuronidation were inhibitory for UGT1A1, 2B7, and 2B17, but activating for UGT1A3. Mixed effects were observed for UGT1A7 and 1A9. Consistent with its inhibitory effects on UGT2B7 activity, warfarin inhibited AZT glucuronidation in HLM ( K i = 74.9–96.3 μM) and RLM ( K i = 190–230 μM). Inhibition of AZT glucuronidation by UGT2B7, HLM, and RLM was also observed with several hydroxylated metabolites of warfarin. Moreover, the systemic exposure (AUC) of AZT in rats was increased by a 1.5- to 2.1-fold upon warfarin coadministration. The elevated AUC was associated with suppressed glucuronidation that was probably attained through a combined action of warfarin and its hydroxylated metabolites. In conclusion, the activities of multiple UGT enzymes can be modulated by warfarin and the nature of modulation was isoform dependent. Also, pharmacokinetic interactions of zidovudine with warfarin were highly possible through inhibition of UGT metabolism.
研究领域:
药理学
·
生物化学
·
临床医学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 4.6
Boyu Fang,Shasha Jin,Wandi Du,Weimin Cai
Background Recent studies have reported a higher risk of bleeding among patients that are co-administrated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and anticoagulant, which raises our concern about the possible TKIs-warfarin pharmacokinetic and pharmacodynamic interaction that could be life-threatening to tumor patients who take warfarin for preventing deep vein thrombosis (DVT). Methods Influences of anlotinib and fruquintinib on the pharmacokinetic and dynamic behavior of warfarin were estimated. Influence on the activity of cytochrome P450 (CYP450) enzymes was detected in vitro through rat liver microsomes. Quantitative analysis of blood concentration in rats was finished by a validated UHPLC-MS/MS method. Furthermore, pharmacodynamic interactions were studied in rats by monitoring prothrombin time (PT) and activated partial thromboplastin time (APTT), while Inferior vena cava (IVC) stenosis-induced DVT model was built to further investigate the antithrombotic effect after co-administration. Results Anlotinib inhibited the activity of cyp2c6, cyp3a1/2 and cyp1a2 in rat liver microsomes in a dose-dependent manner, meanwhile enhanced the AUC 0∼t and AUC 0∼∞ of R-warfarin. However, fruquintinib showed no effects on pharmacokinetics of warfarin. Anlotinib and fruquintinib co-administrated with warfarin was found to exert more significant increase on PT and APTT values than that taking warfarin alone. In IVC stenosis-induced DVT model rats, the co-administration groups significantly reduced the length of thrombus compared with the single warfarin group. Conclusions Anlotinib and fruquintinib enhanced the anticoagulated and antithrombotic effect of warfarin. The anlotinib-induced interaction may due to the inhibition of the metabolism of warfarin. The mechanism of the pharmacodynamic interaction between fruquintinib and warfarin should be further investigated.
研究领域:
肿瘤学
·
药理学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 49
·43724-43731
·
IF 3.289
Yingchun Li,Lu Zhang,Jiang Liu,Shu-Feng Zhou,Khalid Abdullah Al-Ghanim,Shahid Mahboob,Bang-Ce Ye,Xueji Zhang
Warfarin sodium (WFS) is a widely used oral anticoagulant drug but has a narrow therapeutic window. Since traditional detection methods applied for therapeutic drug monitoring suffer some shortcomings, including difficulty in obtaining timely reports, high costs and tedious operation, it is necessary to develop a detection system for the rapid monitoring of WFS in biological samples. Here we report a novel electrochemical sensor, which was facilely fabricated by coupling nanoporous gold leaf (NPGL) with molecularly imprinted polymer (MIP) to afford ultrasensitive and selective determination of WFS. The morphological characterization via scanning electron microscopy proved the successful modification of the sensor by NPGL followed with MIP layer modification. The influencing parameters including the type of monomer, pH and molar ratio of template to monomer were optimized during electro-polymerization. Using Fe(CN)63−/4− as a probe acting as an electrical indicator, a linear relationship of the current response versus the concentration of WFS was obtained in the range from 1.0 × 10−10 to 8.0 × 10−8 M under the optimal experimental conditions, with a detection limit of 4.1 × 10−11 M (S/N = 3). In addition, the as-prepared sensor exhibited specific detection of WFS over its structural analogues and interferents, and the established electrochemical approach was validated using the standard method – high performance liquid chromatography. Eventually, rapid and accurate determination of WFS in human blood was carried out after easy sample pretreatment.
研究领域:
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2025
·
IF 10.9
Pengchen Wang,Jintong Na,Xiyu Liu,Minhui Cui,Ganghao Liang,Xinyue He,Haihua Xiao,Yongxiang Zhao,Yuan Liao,Liping Zhong
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by low immune response rates and high recurrence. This underscores an urgent need for more effective treatment strategies for liver cancer patients. Ferroptosis, a type of cell death associated with iron-dependent lipid peroxidation, has shown significant potential in HCC treatment. However, the efficacy of this monotherapy for tumor treatment remains limited. Enhancing reactive oxygen species (ROS) accumulation and lipid peroxide formation by inhibiting the tumor cell antioxidant system has emerged as a promising anti-tumor strategy. In this study, we developed a nanoplatform, NP (nanoparticle)-BSD@WFR, specifically tailored for HCC treatment. This system combines a biodegradable sonodynamic polymer (BSD) with warfarin (WFR), a VKORC1L1 inhibitor that prevents intracellular peroxide elimination and enhances ferroptosis. Under ultrasound irradiation, NP-BSD@WFR generates ROS and releases WFR, directly targeting cancer cells. Concurrently, ROS and WFR synergistically enhance lipid peroxide production in cancer cells, triggering ferroptosis and activating the immune system. Animal studies further demonstrate that combining sonodynamic therapy with WFR-induced ferroptosis produces a synergistic anti-tumor effect, promoting a strong immune response in vivo. This study introduces an innovative therapeutic approach combining sonodynamic therapy and WFR for HCC treatment and highlights its promising efficacy.
✓ 已验证
产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2021
·
IF 6.707
Miao Fu,Zhiying Feng,Jing Wang,Ying Zhu,Lanlan Gan,Xiaoming Yang
Room-temperature phosphorescence (RTP) materials have harvested enormous attention owing to their advanced optical properties, providing their possibility of the wider applications. Here, we designed a facile strategy to synthesize phosphorus and nitrogen co-doped carbon dots, while creatine provided the carbon and nitrogen source (CDs@creatine). Meanwhile, the as-prepared CDs@creatine exhibited the bright blue fluorescence in aqueous suspension, and showed the green RTP while being fixed on the filter paper. Significantly, the fluorescence of CDs@creatine was quenched by the introduction of warfarin, whereas their RTP was simultaneously enhanced. Specifically, their fluorescence reduction was mainly ascribed to static quenching effect (SQE) and inner filter effect (IFE). In addition, the abundant hydroxyl groups on the surface of CDs@creatine interacted with the carbonyl groups of warfarin to form hydrogen bonds which rigidified the excited triplet against the non-radiative transition, and thus leading to their enhanced phosphorescence. Therefore, a dual-channel detecting strategy of warfarin has been successfully proposed with the fluorescent linear range from 8 × 10 −3 to 8 × 10 −7 M and phosphorescent linear range of 2 × 10 −5 to 1 × 10 −8 M, which established a new way of assaying warfarin. Besides, CDs@creatine served as both fluorescent and phosphorescent ink, and were applied for painting and information encryption.
研究领域:
材料科学
·
分析化学
·
光学材料
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Jiali Gu,Hongrui Liu,Xiyao Huang,Yanxuan Ma,Liang Zhang
Lipid-lowering drugs are often taken with anticoagulant drugs in hyperlipidemia patients. Fenofibrate (FNBT) and warfarin (WAR) are common clinical lipid-lowering drugs and anticoagulant drugs, respectively. A study of binding affinity, binding force, binding distance, and binding sites was performed to determine the interaction mechanism between drugs and carrier proteins (bovine serum albumin, BSA), as well as their effects on BSA conformation. Both FNBT and WAR can form complexes with BSA by van der Waals force and hydrogen bonds. WAR had a stronger fluorescence quenching effect on BSA, a stronger binding affinity, and greater effects on BSA conformation than FNBT. According to fluorescence spectroscopy and cyclic voltammetry, co-administration of drugs decreased one drug's binding constant to BSA and increased its binding distance. This suggested that each drug's binding to BSA was disturbed by each other, as well as each drug's binding ability to BSA was altered by the other. It was demonstrated that co-administration of drugs had greater effects on the secondary structure of BSA and microenvironment polarity surrounding amino acid residues, using multiple spectroscopy techniques, such as ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and synchronous fluorescence spectroscopy.
研究领域:
药理学
·
生物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）