Xanthine Oxidase Inhibitors

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Fan-hao Meng - One of the best experts on this subject based on the ideXlab platform.

  • Design, synthesis and biological evaluation of 1-hydroxy-2-phenyl-4-pyridyl-1H-imidazole derivatives as Xanthine Oxidase Inhibitors.
    European journal of medicinal chemistry, 2018
    Co-Authors: Ting-jian Zhang, Fan-hao Meng, Yu Lei, Dan Liu, Yao Feng, Jiaxing Zhao, Shaolei Chen, Shaojie Wang
    Abstract:

    Abstract In our previous study, we reported a series of 1-hydroxy-2-phenyl-1H-imidazole-5-carboxylic acid derivatives that presented excellent in vitro Xanthine Oxidase inhibitory potency. As a continuation study, a series of 1-hydroxy-2-phenyl-1H-imidazole derivatives containing a pyridine moiety (4a-g and 5a-g) at the 4-position was designed and synthesized. Evaluation of in vitro Xanthine Oxidase inhibition demonstrated that the 4a-g series was more potent than the 5a-g series. Compound 4f was the most promising derivative in the series with an IC50 value of 0.64 μM. A Lineweaver-Burk plot revealed that compound 4f acted as a mixed-type Xanthine Oxidase inhibitor. An iso-pentyloxy group at the 4′-position improved the inhibitory potency. More interestingly, structure-activity relationship analysis indicated that the pyridine para-N atom played a crucial role in the inhibition. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study. In addition, a three dimensional quantitative structure-activity relationships model which possessed reasonable statistics (q2 = 0.885 and r2 = 0.993) was conducted to further understand the structural basis of these compounds as Xanthine Oxidase Inhibitors. These compounds, especially compound 4f, have good potential for further investigations.

  • Design, synthesis, and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as Xanthine Oxidase Inhibitors.
    Chemical biology & drug design, 2017
    Co-Authors: Ting-jian Zhang, Li Songye, Yi Zhang, Fan-hao Meng
    Abstract:

    A series of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives (1a-p) was designed, synthesized, and identified as Xanthine Oxidase Inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC50 values of 8.1 and 6.7 μm, respectively. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type Xanthine Oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom, and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The basis of Xanthine Oxidase inhibition by 1k was rationalized by molecular modeling studies.

  • Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives as Xanthine Oxidase Inhibitors.
    Bioorganic & medicinal chemistry letters, 2017
    Co-Authors: Ting-jian Zhang, Fan-hao Meng, Lin Wang, Li Songye, Yi Zhang, Hua Gao
    Abstract:

    This study mainly focused on the modification of the X2 position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X2 position was designed and synthesized. Evaluation of their inhibitory potency in vitro on Xanthine Oxidase indicated that these compounds exhibited micromolar level potencies, with IC50 values ranging from 0.21µM to 26.13μM. Among them, compound 1s (IC50=0.21μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X2 position could be unfavorable for potency. The Lineweaver-Burk plot revealed that compound 1s acted as a mixed-type Xanthine Oxidase inhibitor. Analysis of the structure-activity relationships demonstrated that a more lipophilic ether tail (e.g., meta-methoxybenzoxy) at the 4'-position could benefit the inhibitory potency. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study.

  • Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent Xanthine Oxidase Inhibitors
    Bioorganic and Medicinal Chemistry Letters, 2017
    Co-Authors: Ting-jian Zhang, Qing Xia Wu, Song-ye Li, Wei-yan Yuan, Su Yang, Qi Sun, Lin Wang, Fan-hao Meng
    Abstract:

    A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel Xanthine Oxidase Inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50values of 0.6 μM and 0.8 μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type Xanthine Oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of Xanthine Oxidase by 1h was rationalized by molecular modeling studies.

Ting-jian Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Design, synthesis and biological evaluation of 1-hydroxy-2-phenyl-4-pyridyl-1H-imidazole derivatives as Xanthine Oxidase Inhibitors.
    European journal of medicinal chemistry, 2018
    Co-Authors: Ting-jian Zhang, Fan-hao Meng, Yu Lei, Dan Liu, Yao Feng, Jiaxing Zhao, Shaolei Chen, Shaojie Wang
    Abstract:

    Abstract In our previous study, we reported a series of 1-hydroxy-2-phenyl-1H-imidazole-5-carboxylic acid derivatives that presented excellent in vitro Xanthine Oxidase inhibitory potency. As a continuation study, a series of 1-hydroxy-2-phenyl-1H-imidazole derivatives containing a pyridine moiety (4a-g and 5a-g) at the 4-position was designed and synthesized. Evaluation of in vitro Xanthine Oxidase inhibition demonstrated that the 4a-g series was more potent than the 5a-g series. Compound 4f was the most promising derivative in the series with an IC50 value of 0.64 μM. A Lineweaver-Burk plot revealed that compound 4f acted as a mixed-type Xanthine Oxidase inhibitor. An iso-pentyloxy group at the 4′-position improved the inhibitory potency. More interestingly, structure-activity relationship analysis indicated that the pyridine para-N atom played a crucial role in the inhibition. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study. In addition, a three dimensional quantitative structure-activity relationships model which possessed reasonable statistics (q2 = 0.885 and r2 = 0.993) was conducted to further understand the structural basis of these compounds as Xanthine Oxidase Inhibitors. These compounds, especially compound 4f, have good potential for further investigations.

  • Design, synthesis, and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as Xanthine Oxidase Inhibitors.
    Chemical biology & drug design, 2017
    Co-Authors: Ting-jian Zhang, Li Songye, Yi Zhang, Fan-hao Meng
    Abstract:

    A series of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives (1a-p) was designed, synthesized, and identified as Xanthine Oxidase Inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC50 values of 8.1 and 6.7 μm, respectively. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type Xanthine Oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom, and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The basis of Xanthine Oxidase inhibition by 1k was rationalized by molecular modeling studies.

  • Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives as Xanthine Oxidase Inhibitors.
    Bioorganic & medicinal chemistry letters, 2017
    Co-Authors: Ting-jian Zhang, Fan-hao Meng, Lin Wang, Li Songye, Yi Zhang, Hua Gao
    Abstract:

    This study mainly focused on the modification of the X2 position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X2 position was designed and synthesized. Evaluation of their inhibitory potency in vitro on Xanthine Oxidase indicated that these compounds exhibited micromolar level potencies, with IC50 values ranging from 0.21µM to 26.13μM. Among them, compound 1s (IC50=0.21μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X2 position could be unfavorable for potency. The Lineweaver-Burk plot revealed that compound 1s acted as a mixed-type Xanthine Oxidase inhibitor. Analysis of the structure-activity relationships demonstrated that a more lipophilic ether tail (e.g., meta-methoxybenzoxy) at the 4'-position could benefit the inhibitory potency. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study.

  • Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent Xanthine Oxidase Inhibitors
    Bioorganic and Medicinal Chemistry Letters, 2017
    Co-Authors: Ting-jian Zhang, Qing Xia Wu, Song-ye Li, Wei-yan Yuan, Su Yang, Qi Sun, Lin Wang, Fan-hao Meng
    Abstract:

    A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel Xanthine Oxidase Inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50values of 0.6 μM and 0.8 μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type Xanthine Oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of Xanthine Oxidase by 1h was rationalized by molecular modeling studies.

  • synthesis of some 5 phenylisoxazole 3 carboxylic acid derivatives as potent Xanthine Oxidase Inhibitors
    ChemInform, 2010
    Co-Authors: Shaojie Wang, Ting-jian Zhang, Jian Wang, Jiarun Chen, Yong Zhao
    Abstract:

    A molecular modeling study is performed on the most promising compound (Va) to gain an insight into its binding mode with Xanthine Oxidase (XO) and to provide the basis for further structure-guided design of new XO Inhibitors.

Ricardo L. E. Furlan - One of the best experts on this subject based on the ideXlab platform.

Chunming Liu - One of the best experts on this subject based on the ideXlab platform.

  • rapid screening and evaluation of xod Inhibitors and o2 scavenger from total flavonoids of ginkgo biloba leaves by lc ms and multi mode microplate reader
    Biomedical Chromatography, 2020
    Co-Authors: Jing Wang, Yong Zhang, Meizhu Zheng, Jing Cui, Chunming Liu, Meiqi Zhou, Zhiqiang Liu, Shu Liu
    Abstract:

    Superoxide anion radical scavenger and Xanthine Oxidase inhibitor play an important role in the treatment of several relevant human diseases. In the present study, ultrafiltration liquid chromatography-mass spectrometry coupled to microplate reader was applied to screen and identify superoxide anion radical scavengers and Xanthine Oxidase Inhibitors from total flavonoids of Ginkgo biloba leaves. As a result, four compounds (quercetin, apigenin, kaempferol and isorhamnetin) were screened as Xanthine Oxidase Inhibitors by ultrafiltration LC-MS, and the 50% scavenging concentration values of the screened flavonoids were lower than those for allopurinol. Lineweaver-Burk plot results indicated that kaempferol was a competitive Xanthine Oxidase inhibitor; the other flavonoids were all anticompetitive Inhibitors. Four flavonoids-rutin, quercetin, kaempferol and isorhamnetin-were screened as superoxide anion radical scavengers by LC-MS. The results demonstrate that the method for screening and evaluation of superoxide anion radical scavenger and Xanthine Oxidase inhibitor from a complex mixture system is feasible and efficient.

  • Screening, separation, and evaluation of Xanthine Oxidase Inhibitors from Paeonia lactiflora using chromatography combined with a multi-mode microplate reader
    Journal of separation science, 2017
    Co-Authors: Jing Wang, Dongfang Shi, Meizhu Zheng, Jing Cui, Chunming Liu, Chengyu Liu
    Abstract:

    Natural products have become one of the most important resources for discovering novel Xanthine Oxidase Inhibitors, which are commonly employed in the treatment of hyperuricemia and gout. However, to date, few reports exist regarding the use of monoterpene glycosides as Xanthine Oxidase Inhibitors. Thus, we herein report the use of ultrafiltration coupled with liquid chromatography in the screening of monoterpene glycoside Xanthine Oxidase Inhibitors from the extract of Paeonia lactiflora (P. lactiflora), and both high-performance counter-current chromatography and medium-pressure liquid chromatography were employed to separate the main constituents. Furthermore, the Xanthine Oxidase inhibitory activities and the mechanisms of inhibition of the isolated compounds were evaluated using a multi-mode microplate reader by Molecular Devices. As a result, three monoterpene glycosides were separated by combined high-performance counter-current chromatography and medium-pressure liquid chromatography in purities of 90.4, 98.0, and 86.3%, as determined by liquid chromatography. These three compounds were identified as albiflorin, paeoniflorin, and 1-O-β-ᴅ-glucopyranosyl-8-O-benzoylpaeonisuffrone by electrospray ionization tandem mass spectrometry, and albiflorin and paeoniflorin were screened as potential Xanthine Oxidase Inhibitors by ultrafiltration with liquid chromatography. The evaluation results of Xanthine Oxidase inhibitory activity corresponded with the screening results, as only albiflorin and paeoniflorin exhibited Xanthine Oxidase inhibitory activity.

  • development of a method to screen and isolate potential Xanthine Oxidase Inhibitors from panax japlcus var via ultrafiltration liquid chromatography combined with counter current chromatography
    Talanta, 2015
    Co-Authors: Ying Tang, Chunming Liu, Liping Guo, Yuchi Zhang
    Abstract:

    Panax japlcus var is a typical Chinese herb with a large number of saponins existing in all parts of it. The common methods of screening and isolating saponins are mostly labor-intensive and time-consuming. In this study, a new assay based on ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) was developed for the rapid screening and identifying of the ligands for Xanthine Oxidase from the extract of P. japlcus. Six saponins were identified as Xanthine Oxidase Inhibitors from the extract. Subsequently, the specific binding ligands, namely, 24 (R)-majoroside R1, chikusetsusaponin IVa, oleanolic acid-28-O-β-D-glucopyranoside, notoginsenoside Fe, ginsenoside Rb2 and ginsenoside Rd (the purities of them were 95.74%, 96.12%, 93.19%, 94.83%, 95.07% and 94.62%, respectively) were separated by high-speed counter-current chromatography (HSCCC). The component ratio of the solvent system of HSCCC was calculated with the help of a multiexponential function model was optimized. The partition coefficient (K) values of the target compounds and resolutions of peaks were employed as the research indicators, and exponential function and binomial formulas were used to optimize the solvent system and flow rate of the mobile phases in a two-stage separation. An optimized two-phase solvent system composed of ethyl acetate, isopropanol, 0.1% aqueous formic acid (1.9:1.0:1.3, v/v/v, for the first-stage) and that composed of methylene chloride, acetonitrile, isopropanol, 0.1% aqueous formic acid (5.6:1.0:2.4:5.2, v/v/v/v, for the second-stage) were used to isolate the six compounds from P. japlcus. The targeted compounds isolated, collected and purified by HSCCC were analyzed by high performance liquid chromatography (UPLC), and the chemical structures of all the six compounds were identified by UV, MS and NMR. The results demonstrate that UF-LC-MS combined with HSCCC might provide not only a powerful tool for screening and isolating Xanthine Oxidase Inhibitors in complex samples but also a useful platform for discovering bioactive compounds for the prevention and treatment of gout.

  • ultrafiltration liquid chromatography combined with high speed countercurrent chromatography for screening and isolating potential α glucosidase and Xanthine Oxidase Inhibitors from cortex phellodendri
    Journal of Separation Science, 2014
    Co-Authors: Chunming Liu, Jing Wang, Liping Guo, Yuchi Zhang, Yueqi Wang, Yumeng Wang, Junqi Ren, Xiaojing Yang, Yao Qin, Ying Tang
    Abstract:

    Cortex Phellodendri is a typical Chinese herb with a large number of alkaloids existing in all parts of it. The most common methods for screening and isolating alkaloids are mostly labor intensive and time consuming. In this study, a new assay based upon ultrafiltration liquid chromatography was developed for the rapid screening of ligands for α-glucosidase and Xanthine Oxidase. The C. Phellodendri extract was found to contain two alkaloids with both α-glucosidase- and Xanthine Oxidase binding activities and one lactone with α-glucosidase-binding activity. Subsequently, with the help of high-speed countercurrent chromatography, the specific binding ligands including palmatine, berberine, and obaculactone with purities of 97.38, 96.12, and 96.08%, respectively, were successfully separated. An optimized low-toxicity two-phase solvent system composed of ethyl acetate/n-butanol/ethanol/water (3.5:1.7:0.5:5, v/v/v/v) was used to isolate the three compounds mentioned above from C. Phellodendri. The targeted compounds were identified by liquid chromatography coupled with mass spectrometry and NMR spectroscopy. Therefore, ultrafiltration liquid chromatography combined with high-speed countercurrent chromatography is not only a powerful tool for screening and isolating α-glucosidase and Xanthine Oxidase Inhibitors in complex samples but is also a useful platform for discovering bioactive compounds for the prevention and treatment of diabetes mellitus and gout.

Yi Dong - One of the best experts on this subject based on the ideXlab platform.

  • in vitro and in vivo studies on adlay derived seed extracts phenolic profiles antioxidant activities serum uric acid suppression and Xanthine Oxidase inhibitory effects
    Journal of Agricultural and Food Chemistry, 2014
    Co-Authors: Mouming Zhao, Dongxiao Sunwaterhouse, Guowan Su, Xiao Wang, Yi Dong
    Abstract:

    This study aimed to explore the potential of polished adlay, brown adlay, adlay bran, and adlay hull to prevent and treat hyperuricemia. Brown adlay extract effectively decreased the serum uric acid levels of oxonate-induced hyperuricemic rats. Free and bound phenolic extracts from these materials contained significant amounts of phenolics, with free phenolics dominated by chlorogenic acid and p-coumaric acid while bound phenolics dominated by p-coumaric acid and ferulic acid. Free and bound phenolics of adlay bran exhibited significant Xanthine Oxidase inhibition activities, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities, oxygen radical absorbance capacities, and superoxide radical scavenging activities. Adlay bran phenolics could be effective Xanthine Oxidase Inhibitors and radical scavengers. p-Coumaric acid is a Xanthine Oxidase inhibitor with strong superoxide radical scavenging activity. However, ferulic acid is a Xanthine Oxidase inhibitor with weak superoxide radical scavenging...

  • in vitro and in vivo studies on adlay derived seed extracts phenolic profiles antioxidant activities serum uric acid suppression and Xanthine Oxidase inhibitory effects
    Journal of Agricultural and Food Chemistry, 2014
    Co-Authors: Mouming Zhao, Dongxiao Sunwaterhouse, Xiao Wang, Dashuai Zhu, Lianzhu Lin, Yi Dong
    Abstract:

    This study aimed to explore the potential of polished adlay, brown adlay, adlay bran, and adlay hull to prevent and treat hyperuricemia. Brown adlay extract effectively decreased the serum uric acid levels of oxonate-induced hyperuricemic rats. Free and bound phenolic extracts from these materials contained significant amounts of phenolics, with free phenolics dominated by chlorogenic acid and p-coumaric acid while bound phenolics dominated by p-coumaric acid and ferulic acid. Free and bound phenolics of adlay bran exhibited significant Xanthine Oxidase inhibition activities, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities, oxygen radical absorbance capacities, and superoxide radical scavenging activities. Adlay bran phenolics could be effective Xanthine Oxidase Inhibitors and radical scavengers. p-Coumaric acid is a Xanthine Oxidase inhibitor with strong superoxide radical scavenging activity. However, ferulic acid is a Xanthine Oxidase inhibitor with weak superoxide radical scavenging activity. Chlorogenic acid is a superoxide radical scavenger with weak Xanthine Oxidase inhibitory activity.