CHIRALITY
·
2021
·Vol. 34
·期 1
·126-133
·
IF 2.437
Dong Guo,Rujian He,Wenxia Su,Ziqing Liang,Weiguang Zhang,Jun Fan
An efficient, sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) chiral analysis method was established for determination of chloroquine and hydroxychloroquine enantiomers in rat liver microsomes. Effects of polysaccharide chiral stationary phases and basic additives on chiral separations of two analytes were discussed in detail. Amylose tris(3, 5-dimethylphenylcarbamate)-coated chiral stationary phase showed the best separation performance for them with acetonitrile-diethylamine-ethanol-diethylamine mixture (90:0.1:10:0.1, v/v/v/v) among four chiral stationary phases. Then, multiple reaction monitoring mode was selected as the data acquisition for determination of two pairs of enantiomers. The proposed LC–MS/MS chiral analysis method was validated in terms of linearity, accuracy, precision, and specificity. Good linearity with correlation coefficient over 0.998 was obtained in the concentration range of 0.05–5 μM. Limits of quantification for chloroquine and hydroxychloroquine enantiomers were 5.0 and 1.0 nM, respectively. The recoveries ranged from 81.14% to 111.09%. The intra-day and inter-day relative standard deviation were less than 6.5%. Moreover, concentrations of chloroquine and hydroxychloroquine enantiomers in rat liver microsomes were determined through the proposed LC–MS/MS analysis method. After incubated with rat liver microsomes for 10 min, the enantiomeric factor of hydroxychloroquine decreased from 0.50 to 0.45 ( p < 0.001). In brief, our developed determination method for chloroquine and hydroxychloroquine enantiomers through LC–MS/MS spectrometry showed the characteristics of high-efficiency, fast speed, and very low detection limit, and would be greatly beneficial for screening and quantitation of them in biological matrices.
研究领域:
药理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2024
·
IF 2.6
Chunyu Yan,Wei Zhou,Yan Zhang,Xuelian Zhou,Qinglong Qiao,Lu Miao,Zhaochao Xu
In this study, super-resolution structured illumination microscope (SIM) was used to analyze molecular mechanism of endocytic acidification inhibitors in the SARS-CoV-2 pandemic, such as Chloroquine (CQ), Hydroxychloroquine (HCQ) and Bafilomycin A1 (BafA1). We fluorescently labeled the SARS-CoV-2 RBD and its receptor ACE2 protein with small molecule dyes. Utilizing SIM imaging, the real-time impact of inhibitors (BafA1, CQ, HCQ, Dynasore) on the RBD-ACE2 endocytotic process was dynamically tracked in living cells. Initially, the protein activity of RBD and ACE2 was ensured after being labeled. And then our findings revealed that these inhibitors could inhibit the internalization and degradation of RBD-ACE2 to varying degrees. Among them, 100 nM BafA1 exhibited the most satisfactory endocytotic inhibition (~63.9%) and protein degradation inhibition (~97.7%). And it could inhibit the fusion between endocytic vesicles in the living cells. Additionally, Dynasore, a widely recognized dynein inhibitor, also demonstrated cell acidification inhibition effects. Together, these inhibitors collectively hinder SARS-CoV-2 infection by inhibiting both the viral internalization and RNA release. The comprehensive evaluation of pharmacological mechanisms through super-resolution fluorescence imaging has laid a crucial theoretical foundation for the development of potential drugs to treat COVID-19.
研究领域:
病毒学
·
细胞生物学
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药理学
·
成像科学
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DOI
PubMed
高影响因子
OPTICAL MATERIALS
·
2021
·
IF 3.08
Qin Tan,Xuanxuan An,Shuang Pan,Shujun Zhen,Yongmei Hu,Xiaoli Hu
Clioquinol (CQ) is not only used to treat skin diseases, but also CQ is a potential pharmaceutical for the treatment of neurodegenerative diseases. However, only a few researches report the detection of CQ. Thus, it is of great significance to accurately quantify CQ. Herein, we developed a CQ fluorescent sensor by Cu 2+ and carbon dots (CDs). Cu 2+ adsorbed on the surface of CDs preventing the non-radiative recombination of the holes in the valence band and the excited electrons in the CDs conduction band , which brings about an increase in the fluorescence intensity of CDs. However, a complex is formed owing to the strong affinity with Cu 2+ and CQ causing that Cu 2+ is disrobed from the CDs surface and then it quenched the fluorescence of CDs through inner filter effect (IFE). The CDs + Cu 2+ system displays preferable sensitivity and high selectivity toward CQ in a range of 40.0–400.0 μmol L −1 with a detection limit of 4.7 μmol L −1 . In addition, the strategy is employed for the quantification of CQ in clioquinol cream with satisfactory results.
研究领域:
分析化学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2023
·
IF 5.4
Lan-Yi Hu,Ye Yuan,Zi-Xuan Wen,Yi-Yue Hu,Miao-Miao Yin,Yan-Jun Hu
Chloroquine (CQ) and hydroxychloroquine (HCQ) show good efficacy in the treatment of SARS-CoV-2 in the early stage, while they are no longer recommended due to their side effects. As an important drug delivery carrier, serum albumin (SA) is closely related to the efficacy of drugs . Here, the affinity behaviour of chloroquine and hydroxychloroquine with two SA were investigated through the multispectral method of biochemistry and computer simulation. The results showed that the intrinsic emission of both SA was quenched by CQ and HCQ in a spontaneous exothermic entropy reduction static process, which relied mainly on hydrogen bonding and van der Waals forces . The lower binding constants suggested weak binding between the two drugs and SA, which might lead to differences in efficacy and possibly even to varying side effects. Binding site recognition demonstrated that CQ preferred to bind to the two sites of both SA, while HCQ tended to bind to site I of SA. The results of conformational studies demonstrated that CQ and HCQ could affect the structure of both SA by slightly increasing the α -helix content of SA. Finally, we combine the results from experimental start with molecular simulations to suggest drug modifications to guide the design of drugs. This work has important implications for guiding drug design improvements to select CQ derivatives with fewer side effects for the treatment of COVID-19.
研究领域:
药理学
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生物化学
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分子生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 37
·5854-5859
·
IF 4.776
Yan Ma,Huajian Chen,Baimei Hao,Junhong Zhou,Gang He,Zhaohua Miao,Yan Xu,Li Gao,Wei Zhou,Zhengbao Zha
Insufficient and heterogeneously distributed heat commonly leads to the incomplete elimination and recurrence of tumors. Inspired by the fact that autophagy is essential for cell survival in response to harmful stresses, a near-infrared (NIR) light responsive chloroquine (CQ, a well-known autophagy inhibitor) delivery system, consisting of phase-changing material (1-tetradecanol, PCM) and hollow mesoporous Prussian blue nanoparticles (HMPBs), is reported here to deliver CQ to the tumor region to augment the efficacy of photothermal therapy (PTT). In vitro thermosensitive CQ release assays demonstrated that precise “on–off” release profiles of CQ could be readily manipulated, owing to the excellent photothermal conversion abilities of HMPBs and the solid-to-liquid phase change properties of the PCM under NIR light illumination. Furthermore, targeted autophagy inhibition in cancer cells could remarkably amplify the cell-killing efficiency of PTT, leading to synergistic cancer suppression at mild therapeutic temperatures. Therefore, this work is expected to depict an effective strategy for the design and construction of a thermally responsive CQ delivery platform for modulating autophagy inhibition in tumors to reinforce the efficacy of PTT.
研究领域:
肿瘤学
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纳米医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
CHIRALITY
·
2024
·Vol. 36
·期 5
·e23672
·
IF 2.8
Chen Chen,Yangfeng Peng,Yongming Wei,Mengyuan Liu,Yu Wang,Siqi Xiong,Huiyi Li,Quan He
Hydroxychloroquine (HCQ), 2-([4-([7-Chloro-4-quinolyl]amino)pentyl]ethylamino)ethanol, exhibited significant biological activity, while its side effects cannot be overlooked. The RP-HPLC enantio-separation was investigated for cost-effective and convenient optical purity analysis of HCQ. The thermodynamic resolution of Rac-HCQ, driven by enthalpy and entropy, was achieved on the C18 column using Carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral mobile phase agent (CMPA). The effects of C CM-β-CD , pH, and triethylamine (TEA) V% on the enantio-separation process were explored. Under the optimum conditions at 24°C, the retention times for the two enantiomers were t R 1 = 29.39 min $$ {t}_{R1}=29.39\ \min $$ and t R 2 = 32.42 min $$ {t}_{R2}=32.42\ \min $$ , resulting in R s = 1.87 $$ {R}_s=1.87 $$ . The resolution via diastereomeric salt formation of Rac-HCQ was developed to obtain the active pharmaceutical ingredient of single enantiomer S-HCQ. Di-p-Anisoyl-L-Tartaric Acid (L-DATA) was proved effective as the resolution agent for Rac-HCQ. Surprisingly, it was found that refluxing time was a key fact affecting the resolution efficiency, which meant the kinetic dominate during the process of the resolution. Four factors—solvent volume, refluxing time, filtration temperature, and molar ratio—were optimized using the single-factor method and the response surface method. Two cubic models were established, and the reliability was subsequently verified. Under the optimal conditions, the less soluble salt of 2L-DATA:S-HCQ was obtained with a yield of 96.9% and optical purity of 63.0%. The optical purity of this less soluble salt increases to 99.0% with a yield of 74.2% after three rounds recrystallization.
研究领域:
药物化学
·
分析化学
·
制药工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CATALYSIS LETTERS
·
2024
·Vol. 155
·期 1
·1-16
·
IF 2.3
Huang Yeqiong,Song Zhi,Liu Boxia,Zhang Xiayan,Liu Jialu,Li Cheng,Han Dongxu,Xing Chuhan
After the outbreak of COVID-19, the severe threat to the entire biological environment caused by the extensive use of chloroquine phosphate (CQ) continues. In this paper, a new sol–gel method was used to inject highly active Co into the PrSmMnO 3 matrix structure to prepare a novel perovskite composite catalyst PrSmCo 0.8 Mn 0.2 O 3 with stable properties, and was used to efficiently activate monopersulfate (PMS) to produce high concentration of 1 O 2 and degrade CQ. The CQ degradation rate of 40 mg L −1 within 80 min was 97.3%, and excellent performance was maintained after 5 cycles. The fixed variable method found that the PrSmCo 0.8 Mn 0.2 O 3 /PMS system still has high efficiency and adaptability in complex water bodies. Through quenching experiments and electron paramagnetic resonance spectroscopy (EPR), we explored the PrSmCo 0.8 Mn 0.2 O 3 /PMS system. PMS is efficiently adsorbed on highly active Co, forming a high-entropy mixed interface, which promotes the decomposition of PMS and generates a large amount of ⋅O 2 − radicals. At the same time, Co–Mn synergistically and efficiently utilizes excess electrons and ⋅O 2 − radicals in the solution to produce high concentrations of 1 O 2 through disproportionation reactions, promoting the degradation of CQ. It provides new insights into the application of perovskite oxides in medical wastewater treatment. Graphical
研究领域:
环境科学
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材料科学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2022
·Vol. 36
·期 20
·e9358
·
IF 2.586
Donghai Xu,Fangfang Pan,Hao Ruan,Nan Sun
Rationale Hydroxychloroquine sulfate is effective in the treatment of malaria and autoimmune diseases and as an antiviral drug. However, unreported impurities are often detected in this drug, which pose a health risk. In this study, the structures of hydroxychloroquine and six unknown impurities were analyzed using ultra-high-performance liquid chromatography-quadrupole/time-of-flight-tandem mass spectrometry (UHPLCQ/TOF/MS/MS), and the structures were characterized using liquid chromatography-solid-phase extraction-nuclear magnetic resonance (LC-SPE-NMR) spectroscopy. Methods An Agilent InfinityLad Poroshell HPH-C18 column (100 × 4.6 mm, 2.7 μm) was used. For the analysis of hydroxychloroquine and six unknown impurities, the mobile phase was 20 mM ammonium formate aqueous solution and methanol/acetonitrile (80:20, v/v) using gradient elution. Full-scan MS and MS 2 were performed to obtain as much structural information as possible. In addition, six unknown impurities were separated by semipreparative liquid chromatography and characterized using LC-SPE-NMR. Results The MS 2 fragmentation patterns of the impurities were investigated, leading to more structural information and an understanding of the fragmentation pathways of the impurities. The structures of the unknown impurities were confirmed using NMR. In addition, some possible pathways of the formation of the impurities in the drugs were outlined, and these impurities were found to be process impurities. Conclusions Based on the identification and characterization of these impurities, this study also describes the cause of the production of the impurities and provides insights for companies to improve their production processes and a scientific basis for the improvement of the related pharmacopoeias.
研究领域:
药学
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分析化学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Feilong Dong,Jinzhe Li,Qiufeng Lin,Da Wang,Cong Li,Yi Shen,Tao Zeng,Shuang Song
Chloroquine (CLQ) is required to manufacture on a larger scale to combat COVID-19. The wastewater containing CLQ will be discharged into the natural water, which was resistant to environmental degradation. Herein, the degradation of CLQ by ferrate (Fe(VI)) was investigated, and the biodegradability of the oxidation products was examined to evaluate the potential application in natural water treatment. The reaction between CLQ and Fe(VI) was pH-dependent and followed second-order kinetics. The species-specific rate constant of protonated Fe(VI) species (HFeO 4 − ) was higher than that of the FeO 4 2− species. Moreover, increasing the reaction temperature could increase the degradation rate of CLQ. Besides, HCO 3 − had positive effect on CLQ removal, while HA had negative effect on CLQ removal. But the experiments shows Fe(VI) could be used as an efficient technique to degrade co-existing CLQ in natural waters. During the oxidation, Fe(VI) attack could lead to aromatic ring dealkylation and chloride ion substitution to form seven intermediate products by liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) determination. Finally, a pure culture test showed that the oxidation of CLQ by Fe(VI) could slightly increase the antimicrobial effect towards Escherichia coli (E.coli) and reduce the toxicity risk of intermediates. These findings might provide helpful information for the environmental elimination of CLQ.
研究领域:
环境科学
·
药理学
·
化学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 23
·8134
·
IF 4.927
Ran Lu,Wei Wang,Bo Dong,Chao Xu,Bo Li,Yong Sun,Junchao Liu,Biao Hong
Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.Keywords:self-assembled CuCo2S4nanocrystals;chloroquine;arterial inflammation;photothermal therapy;chemotherapy
研究领域:
纳米技术
·
生物医学工程
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Weiming Xiang,Fahao Xu,Dong Wan,Xing Wang,Fan Luo,Yong Chen
Chloroquine phosphate (CQ) is an antiviral drug for Coronavirus Disease 2019 and an old drug for treatment of malaria, which has been detected in natural waters. Despite its prevalence, the environmental fate of CQ remains unclear. In this study, the direct photodegradation of CQ under simulated sunlight was investigated. The effect of various parameters such as pH, initial concentration and environmental matrix were examined. The photodegradation quantum yield of CQ (4.5 × 10 −5 −0.025) increased with the increasing pH value in the range of 6.0–10.0. The electron spin resonance (ESR) spectrometry and quenching experiments verified that the direct photodegradation of CQ was primarily associated with excited triplet states of CQ ( 3 CQ*). The common ions had negligible effect and humic substances exhibited a negative effect on CQ photodegradation. The photoproducts were identified using high-resolution mass spectrometry and the photodegradation pathway of CQ was proposed. The direct photodegradation of CQ involved the cleavage of the C–Cl bond and substitution of the hydroxyl group, followed by further oxidation to yield carboxylic products. The photodegradation processes were further confirmed by the density functional theory (DFT) computation for the energy barrier of CQ dichlorination. The findings contribute to the assessment of the ecological risk associated with the overuse of Coronavirus drugs during global public health emergencies.
研究领域:
环境科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 187
·期 1
·1-10
·
IF 5.479
Ding Wen,Yu Tao,Du Yingxiang,Sun Xiaodong,Feng Zijie,Zhao Shiyuan,Ma Xiaofei,Ma Mingxuan,Chen Cheng
Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory.
Schematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.
研究领域:
分析化学
·
药学
·
材料科学
✓ 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）