Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays
Xanthine oxidase (XO) is an enzyme involved in the oxidative process of hypoxanthine and xanthine to uric acid (UA). This process also produces reactive oxygen species (ROS) as byproducts. Both UA and ROS are dangerous for human health, and some health conditions trigger upregulation of XO activity,...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2673-401X/3/4/26 |
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| author | Miguel F. S. de Abreu Camila A. Wegermann Millena S. Ceroullo Isabella G. M. Sant’Anna Renato C. S. Lessa |
| author_facet | Miguel F. S. de Abreu Camila A. Wegermann Millena S. Ceroullo Isabella G. M. Sant’Anna Renato C. S. Lessa |
| author_sort | Miguel F. S. de Abreu |
| collection | DOAJ |
| description | Xanthine oxidase (XO) is an enzyme involved in the oxidative process of hypoxanthine and xanthine to uric acid (UA). This process also produces reactive oxygen species (ROS) as byproducts. Both UA and ROS are dangerous for human health, and some health conditions trigger upregulation of XO activity, which results in many diseases (cancer, atherosclerosis, hepatitis, gout, and others) given the worsened scenario of ROS and UA overproduction. So, XO became an attractive target to produce and discover novel selective drugs based on febuxostat, the most recent XO inhibitor out of only two approved by FDA. Under this context, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) have been successfully applied to rapidly and easily screen for bioactive compounds, isolated or in complex natural matrixes, that act as enzyme inhibitors through the use of an immobilized enzyme reactor (IMER). This article’s goal is to present advances comprising febuxostat-based XO inhibitors as a new trend, bifunctional moieties capable of inhibiting XO and modulating ROS activity, and in-flow techniques employing an IMER in HPLC and CE to screen for synthetic and natural compounds that act as XO inhibitors. |
| first_indexed | 2024-03-09T16:00:52Z |
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| id | doaj.art-feb1c22dc921497c9ae8e2235b75aa87 |
| institution | Directory Open Access Journal |
| issn | 2673-401X |
| language | English |
| last_indexed | 2024-03-09T16:00:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Organics |
| spelling | doaj.art-feb1c22dc921497c9ae8e2235b75aa872023-11-24T17:11:18ZengMDPI AGOrganics2673-401X2022-10-013438041410.3390/org3040026Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening AssaysMiguel F. S. de Abreu0Camila A. Wegermann1Millena S. Ceroullo2Isabella G. M. Sant’Anna3Renato C. S. Lessa4Departamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, BrazilDepartamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, BrazilDepartamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, BrazilDepartamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, BrazilDepartamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, BrazilXanthine oxidase (XO) is an enzyme involved in the oxidative process of hypoxanthine and xanthine to uric acid (UA). This process also produces reactive oxygen species (ROS) as byproducts. Both UA and ROS are dangerous for human health, and some health conditions trigger upregulation of XO activity, which results in many diseases (cancer, atherosclerosis, hepatitis, gout, and others) given the worsened scenario of ROS and UA overproduction. So, XO became an attractive target to produce and discover novel selective drugs based on febuxostat, the most recent XO inhibitor out of only two approved by FDA. Under this context, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) have been successfully applied to rapidly and easily screen for bioactive compounds, isolated or in complex natural matrixes, that act as enzyme inhibitors through the use of an immobilized enzyme reactor (IMER). This article’s goal is to present advances comprising febuxostat-based XO inhibitors as a new trend, bifunctional moieties capable of inhibiting XO and modulating ROS activity, and in-flow techniques employing an IMER in HPLC and CE to screen for synthetic and natural compounds that act as XO inhibitors.https://www.mdpi.com/2673-401X/3/4/26enzyme inhibitiondrug developmentdrugs screeningallopurinolfebuxostatY-700 |
| spellingShingle | Miguel F. S. de Abreu Camila A. Wegermann Millena S. Ceroullo Isabella G. M. Sant’Anna Renato C. S. Lessa Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays Organics enzyme inhibition drug development drugs screening allopurinol febuxostat Y-700 |
| title | Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays |
| title_full | Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays |
| title_fullStr | Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays |
| title_full_unstemmed | Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays |
| title_short | Ten Years Milestones in Xanthine Oxidase Inhibitors Discovery: Febuxostat-Based Inhibitors Trends, Bifunctional Derivatives, and Automatized Screening Assays |
| title_sort | ten years milestones in xanthine oxidase inhibitors discovery febuxostat based inhibitors trends bifunctional derivatives and automatized screening assays |
| topic | enzyme inhibition drug development drugs screening allopurinol febuxostat Y-700 |
| url | https://www.mdpi.com/2673-401X/3/4/26 |
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