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RSC Advances · 2022 ·Vol. 12 ·期 17 ·10460-10466 · IF 4.036

Synthesis of benzoin under supramolecular catalysis involving cyclodextrins in water: application for the preparation of the antiepileptic drug phenytoin

Zhichao Jin,Chunhua Yan,Huimin Chu,Qing Huang,Zhizhong Wang

Among the cyclodextrins screened for the synthesis of 2-hydroxy-1,2-diphenylethanone (benzoin) in water, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) exhibited the highest yield in the benzoin condensation reactions, and HP-β-CD can be recycled several times with little loss of activity through the addition of fresh VB1. As an example of supramolecular catalysis, the methodology was applied to the “green” synthesis of the antiepileptic drug phenytoin through benzoin condensation, oxidation, and cyclization reactions in the presence of HP-β-CD, without the use of any harmful organic solvent. Moreover, the complexation behaviors of HP-β-CD with benzaldehyde and intermediates were studied by UV-vis and 2D-ROESY NMR spectroscopies to reveal the plausible mechanisms of the reactions, and HP-β-CD did not act as a simple phase transfer agent.

研究领域: 有机化学 · 药物化学 · 绿色化学
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ULTRASONICS SONOCHEMISTRY · 2024 · IF 8.7

An improved ultrasound-assisted synthesis of phenytoin suitable for undergraduate education

Baowei Yang,Xiandong Zhai,Runzhe Mei,Pu Wang,Yicheng Mei

A convenient and efficient method for undergraduate student experiments involves the one-pot synthesis of phenytoin from benzoin. This method utilized ultrasonic irradiation in the presence of basic catalyst at room temperature and atmospheric pressure, resulting in shortened reaction times, good yields, and excellent reproducibility. By employing a low-cost ultrasonic cleaner for ultrasonic irradiation in student experiments, the need for expensive equipment investment during the teaching process can be minimized. Consequently, this approach is suitable for widespread promotion and application in undergraduate education.

CAS / MDL: 67-68-5 141-78-6
研究领域: 化学教育 · 有机合成 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICO-BIOLOGICAL INTERACTIONS · 2021 · IF 5.194

Risk prediction of drug-drug interaction potential of phenytoin and miconazole topical formulations

Wei Li,Zhen Wang,Xiaoyu Wang,Xiaowei Cao,Caili Bi,Lili Jiang,Shuna Cui,Yong Liu

The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear. The present investigation conducted in vitro - in vivo extrapolation to predict the potential risks. Our data indicated that miconazole potently inhibited phenytoin hydroxylation in both pooled human liver microsomes (HLMs) and recombinant cytochrome P450 2C9 (CYP2C9) with the K i values of 125 ± 7 nM and 30 ± 2 nM, respectively. Quantitative prediction of DDI risk suggests that, beside intravenous administration or swallowed tablet, combination of phenytoin and miconazole high dose oral gel or buccal tablet may also result in a clinically significant increase of phenytoin AUC (>53%) by the inhibition of miconazole against phenytoin hydroxylation, consequently a higher frequency of adverse events, while the coadministration of miconazole vaginal formulation and phenytoin will be safe.

CAS / MDL: 57-41-0
研究领域: 药理学 · 临床药学 · 药物代谢
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICO-BIOLOGICAL INTERACTIONS · 2022 · IF 5.168

Potential herb-drug interaction risk of thymoquinone and phenytoin

Zhen Wang,Xiaoyu Wang,Zhe Wang,Xin Lv,Hang Yin,Wei Li,Wenli Li,Lili Jiang,Yong Liu

Thymoquinone is a main bioactive compound of Nigella sativa L. ( N.sativa ), which has been used for clinical studies in the treatment of seizures due to its beneficial neuroprotective activity and antiepileptic effects. It has been evidenced that thymoquinone may inhibit the activity of cytochrome P450 2C9 (CYP2C9). However, little is known about the effect of thymoquinone or N.sativa on the pharmacokinetic behavior of phenytoin , a second-line drug widely used in the management of status epilepticus . In this study, we systematically investigated the risk of the potential pharmacokinetic drug interaction between thymoquinone and phenytoin. The inhibitory effect of thymoquinone on phenytoin hydroxylation activity by CYP2C9 was determined using UPLC-MS/MS by measuring the formation rates for p -hydroxyphenytoin ( p -HPPH). The potential for drug-interaction between thymoquinone and phenytoin was quantitatively predicted by using in vitro-in vivo extrapolation (IVIVE). Our data demonstrated that thymoquinone displayed effective inhibition against phenytoin hydroxylation activity. Enzyme kinetic studies showed that thymoquinone exerted a competitive inhibition against phenytoin hydroxylation with a K i value of 4.45 ± 0.51 μM. The quantitative prediction from IVIVE suggested that the co-administration of thymoquinone (>18 mg/day) or thymoquinone-containing herbs ( N.sativa > 1 g/day or N.sativa oil >1 g/day) might result in a clinically significant herb-drug interactions. Additional caution should be taken when thymoquinone or thymoquinone-containing herbs are co-administered with phenytoin, which may induce unexpected potential herb-drug interactions via the inhibition of CYP2C9.

研究领域: 药理学 · 临床医学 · 生物化学
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BIOMATERIALS · 2015 · IF 8.557

A two-photon fluorescent sensor revealing drug-induced liver injury via tracking γ-glutamyltranspeptidase (GGT) level in vivo

Peisheng Zhang,Xiao-fang Jiang,Xuezheng Nie,Yong Huang,Fang Zeng,Xitao Xia,Shuizhu Wu

Currently drug-induced liver injury (DILI) has become a major and challenging public health issue in terms of medicine development and clinical therapy. The level of γ-glutamyl transpeptidase (GGT) has long been regarded as a preclinical/clinical biomarker for prediction of DILI. Herein, we report a two-photon fluorescent sensor for tracking GGT level changes resulted from DILI in vivo. The sensor was prepared by linking a glutamic acid to a dicyanomethylene-4H-pyran (DCM) derivative; and the presence of GGT cleaves γ-glutamyl amide group from the sensor and thereby restores the fluorescence emission (at 635 nm) of DCM moiety under femtosecond pulses at 800 nm. This two-photon sensor exhibits superior sensing performance such as red emission, high photostability and low detection limit (∼0.057 U/L). On a two-photon microscope, the sensor shows a bright red fluorescence in GGT-overexpressing A2780 cells; and it can fluorescently respond to the GGT generated in the liver of zebrafishes as a result of clinical drug (phenytoin) treatment. These findings demonstrate that a commonly-used clinical drug phenytoin can cause remarkable elevation in GGT level in liver, and this sensor may be useful as a marker to detect clinical drug-induced organ damages.

研究领域: 药理学 · 医学成像 · 毒理学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2020 · IF 5.977

Surface molecularly imprinted polymer based on core-shell Fe3O4@MIL-101(Cr) for selective extraction of phenytoin sodium in plasma

Mengtian Jia,Yanyan Zhu,Dong Guo,Xiaogang Bi,Xiaohong Hou

Core-shell magnetic Fe 3 O 4 @MIL-101(Cr) nanoparticles were synthesized via layer-by-layer self-assembly method. Using Fe 3 O 4 @MIL-101(Cr) as support, Fe 3 O 4 @MIL-101(Cr)@MIP was prepared with phenytoin as template, acrylamide as functional monomer , ethylene glycol dimethacrylate as cross-linker, methanol and acetonitrile as porogen , azoisobutyronitrile as initiator. The materials were characterized by a serious of characterization experiments. The prepared Fe 3 O 4 @MIL-101(Cr)@MIP was demonstrated to possess good separability, large adsorption capability, excellent adsorption selectivity , good durability and reusability via adsorption experiments. Subsequently, a magnetic solid phase extraction method (MSPE) based on Fe 3 O 4 @MIL-101(Cr)@MIP combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) was established for the determination of phenytoin sodium in plasma samples. Experimental parameters including pH, the amount of adsorbent, extraction time, elution conditions, the concentration of NaCl were investigated to optimize extraction process. The method was validated. The linearity was observed in the range of 0.05–40 μg mL −1 with a lower limit of quantification of 0.05 μg mL −1 . The calibration equations were y = 0.2514x + 0.0319 ( r 2  = 0.9938), y = 0.2888x + 0.0472 ( r 2  = 0.9943), y = 0.2565x + 0.0418 ( r 2  = 0.9976), respectively. The recoveries ranged from 89.2 to 94.3%, intra- and inter-day precision (RSDs) ranged from 2.1 to 9.7% and 2.9–9.2%, respectively. The established MSPE-HPLC-UV method was time-saving, sensitive, accurate, environmental friendly, and drastically reduced the complex matrix interferences. The established method was successfully applied for phenytoin sodium determination in real plasma samples, providing new directions for therapeutic drug monitoring.

CAS / MDL: 630-93-3 57-41-0
研究领域: 分析化学 · 材料科学 · 药物分析
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

α-Lipoic Acid-Based Nanozyme for Treating Acute Epilepsy

Yage Sun,Xinrui Zhao,Rong Yang,Meng Xiao,Wenguang Liu

Anti-epilepsy drugs (AEDs), a common therapeutic approach for clinically treating epilepsy, suffer from low permeability toward the blood-brain barrier (BBB), side effect risks, and a failure to regulate the pathological microenvironment. These issues hinder the complete control of epilepsy and lead to a vicious cycle of inflammation-epileptogenesis. Herein, an α-lipoic acid (LA)-based nanozyme that loads phenytoin (PHT) and complexes calcium ions (LA@PHT-Ca 2+ ) is developed. This nanozyme combines the functions of delivering AEDs across the BBB and regulating undesirable microenvironments to treat epilepsy. Amphipathic LA self-assembles into stable nanoparticles in water with BBB crossing ability endowed by the transporting of LA through sodium-dependent multivitamin transporter. LA's enzyme-like and redox functions provide LA@PHT-Ca 2+ with excellent scavenging effects on several free radicals via cascade reactions, thereby protecting neurons from oxidative stress. Moreover, Ca 2+ disrupts neuronal respiration, resulting in reduced production of bioenergetic adenosine triphosphate and an improved hypoxic microenvironment. This leads to decreased expression of P-glycoprotein, a drug-efflux gating protein. This novel lipoic acid-based nanozyme, with intrinsic BBB crossing capability, prolonged intracellular drug retention time, and the ability to block the inflammation-epileptogenesis cycle, presents a satisfactory therapeutic effect in epileptic rats, resulting in attenuated symptoms and an improved microenvironment.

研究领域: 神经科学 · 药学 · 纳米技术 · 生物化学
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-11 · IF 15.7

Solvent-free fabrication of ultrathin two-dimensional metal oxides/sulfides in a fixed interlayer by geometric confinement

Wang Weixue,Liu Yang,Du Xinjie,Wang Huihui,Ai Yuejie,Liu Qianwei,Wang Xiangke,Chen Zhe

Two-dimensional (2D) nanomaterials display unique characteristics owing to their ultrahigh surface-to-volume ratio and quantum confinement effects. Nonetheless, seeking a versatile and facile method to rationally shape ultrathin 2D frameworks is still an appealing challenge. Herein, a series of ultrathin 2D metal oxide crystals (2D MOs), including 3d transition metals (Ti, Cr, Mn, Fe, Co, Ni, Cu, Zr, W), lanthanide (Ce) and nontransition metal (In, Sn, Bi) oxides, were created through a confined interlayer growth strategy in combination with melt infiltration, in which no complicated chemistry or sophisticated equipment was needed. The 2D oxides presented lamellar constructions with high crystallinity, and the thickness was strictly limited to ~ 1 nm. The crystallization process, including the Frank-van der Merwe mode and the Volmer-Weber mode, was described. The defects and distortions of 2D TiO 2 reduced the optical band gap and improved the sunlight utilization efficiency, thus accelerating the photocatalytic activity. This method could be extended to the preparation of 2D polymetallic oxides, metal sulfides etc., which enables the development of versatile systems for ultrathin 2D frameworks, especially for nonlayered structures originally.

研究领域: 材料科学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED CATALYSIS B-ENVIRONMENTAL · 2018 · IF 11.698

Cu-Al2O3-g-C3N4 and Cu-Al2O3-C-dots with dual-reaction centres for simultaneous enhancement of Fenton-like catalytic activity and selective H2O2 conversion to hydroxyl radicals

Suqian Xu,Hanxu Zhu,Wenrui Cao,Zhibin Wen,Jinnan Wang,Corvini Philippe François-Xavier,Thomas Wintgens

Cu-Al 2 O 3 -g-C 3 N 4 and Cu-Al 2 O 3 -C-dots were synthesized for the first time to enhance the catalytic activity and utilization of H 2 O 2 . SEM, TEM, XPS, FT-IR, XRD, TPR and solid-state EPR were used to characterize the catalysts. In the Cu-Al 2 O 3 -g-C 3 N 4 system, the electron-rich centre of Cu and electron-deficient site of Al were formed due to the higher electronegativity of Cu. Moreover, Cu ions could coordinate with the hydroxyl on the tri-s-triazine ring of g-C 3 N 4 or the graphene conjugated π-domains of C-dots via the Cu O C linkage so that the orbital interactions involving electron transport from π → Cu also induced the formation of an electron-rich Cu centre and an electron-deficient π-electron conjugated system, resulting in the strengthening of the dual-reaction centres. This mechanism was validated by Roman, EPR and XPS spectra. In addition, EPR experiments demonstrated that two electron-transfer processes formed OH in the presence of H 2 O 2 . The first electron transfer was from the electron-rich Cu centres to H 2 O 2 , and the other was from H 2 O to the electron-deficient site. Thus, more OH were generated and high H 2 O 2 utilization was achieved in the Cu-Al 2 O 3 -g-C 3 N 4 and Cu-Al 2 O 3 -C-dots suspension. Furthermore, the turnover frequency (TOF) for the Cu-Al 2 O 3 -C-dots and Cu-Al 2 O 3 -g-C 3 N 4 dispersions were determined and were found to be much higher than those of the classic homogeneous Fenton reaction. Thus, Cu-Al 2 O 3 -g-C 3 N 4 and Cu-Al 2 O 3 -C-dots showed high activity and stability for the catalytic degradation of organic pollutants under mild conditions.

研究领域: 环境科学 · 材料科学
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BIOMEDICAL CHROMATOGRAPHY · 2018 ·Vol. 33 ·期 4 ·e4454 · IF 1.688

Effects of Danhong injection, a traditional Chinese medicine, on nine cytochrome P450 isoforms in vitro

Jing-Xian Zhang,Mei-Juan Qi,Mei-Zhi Shi,Jun-Jun Chen,Xiang-Qi Zhang,Jiao Yang,Ke-Zhi Zhang,Yong-Long Han,Cheng Guo

Danhong injection (DHI) is made from Salvia miltiorrhiza Bunge. and Carthamus tinctorius L. extract and is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. This study aimed to evaluate the effect of DHI on cytochrome P450 (CYP450) enzymes in vitro to predict drug–drug interactions based on CYP450 as combination therapy. To assess the inhibitory effect of DHI on CYP450, we detected the IC 50 value of DHI on CYP450 in vitro by liquid chromatography/tandem mass spectrometry (LC–MS/MS). Simultaneously, the induction effect of DHI on CYP450s was also evaluated. The relative induction ratios of DHI on CYP1A2, CYP2B6 and CYP3A4 activity were calculated by LC–MS/MS. The expression level of CYP3A4 mRNA was determined by reverse transcription PCR (RT-PCR). The LC–MS/MS data showed DHI intensively inhibit CYP2A6 activity and the intensity of inhibition was followed by CYP2C8, CYP3A4, CYP2C19, CYP2B6, CYP2D6, CYP1A2, CYP2E1 and CYP2C9 in vitro . The results of RT-PCR showed that there is a certain induction of DHI on CYP3A4 mRNA in human primary hepatocytes in vitro . The study suggested that drug–drug interactions might occur in clinical co-administration of drugs owing to the CYP2A6 inhibition and CYP3A4 induction.

研究领域: 药理学 · 临床医学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Environmental Science-Nano · 2023 ·Vol. 10 ·期 5 ·1284-1296 · IF 7.3

Reconstructing atomic Fe coordination in the PMS activation process to realize efficient BPA degradation at low temperature

Yuxuan Lin,Weihua Qin,Yuwei Lu,Mingye Ren,Pan Gao,Feng Xiao,Shaoxia Yang

Improving the performance of single-atom catalysts (SACs) is still challenging in Fenton-like reactions for degrading refractory organic pollutants. Here, we designed P and N co-doped Fe SACs to regulate the electronic structure of Fe active sites and enhance the reaction kinetics of peroxymonosulfate (PMS) activation. The obtained heteroatom-doped Fe SACs for the first time exhibited an ultra-low activation energy (ca. 3.7 kJ mol−1) and excellent degradation efficiency for bisphenol A (BPA) in a wide pH range (4.3–9.2). The superior reaction kinetics of the Fe SACs were attributed to enriching the electron density of atomic Fe and then forming dual electron-rich/-deficient sites, which accelerated the electron transformation to generate reactive oxygen species (ROS). In this study the heteroatom-doped Fe SACs with rapid reaction kinetics are achieved, and provides an idea to design SACs with superior performance in heterogeneous Fenton-like reactions.

研究领域: 环境科学 · 催化 · 化学工程 · 材料科学
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JOURNAL OF MOLECULAR LIQUIDS · 2023 · IF 6

Ionic liquid microcapsules for the topical delivery of pterostilbene: Enhanced transdermal delivery and anti-wrinkle and skin brightening effects

De Bai,Haowei Chen,Lijuan Liu,Nanxi Xiang,Jichuan Zhang,Chengyu Wu,Jiaheng Zhang,Fang Wang

Pterostilbene (PTB) is a hydrophobic compound derived from plants in the Astragalus family. PTB possesses remarkable skin brightening and antioxidant properties. However, delivery methods for PTB require enhancement, and this can be achieved by formulating suitable carriers. In this study, we prepared ionic liquid microcapsules containing PTB by using a microencapsulation technique based on a matrine and cocinic acid ([Mat][Coc]) ionic liquid. The particle size of the microcapsules was 154.5 ± 3.42 nm, and the encapsulation efficiency was as high as 99.7 %. Further, the PTB-loaded ionic liquid microcapsules had good biocompatibility, enhanced skin retention (7.7-times higher than that of free PTB), and improved skin penetration without damaging the skin structure. Clinical testing with human subjects revealed that the microcapsule emulsion reduced fine lines and brightened skin tone. Therefore, PTB-loaded ionic liquid microcapsules have promise for use in cosmetic formulations and applications in transdermal drug delivery and efficacy enhancement.

CAS / MDL: 56-81-5 57-41-0
研究领域: 药剂学 · 化妆品科学 · 药物递送系统 · 纳米技术
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