Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure-Based Drug Design

Giuseppe Luna, Anton V. Dolzhenko, Ricardo L. Mancera

    Research output: Contribution to journalReview ArticleOtherpeer-review

    27 Citations (Scopus)

    Abstract

    Xanthine oxidase (XO) is the enzyme responsible for the catabolism of purines and their conversion into uric acid. XO is thus the target for the treatment of hyperuricemia and gout. For more than 50 years the only XO inhibitor drug available on the market was the purine analogue allopurinol. In the last decade there has been a resurgence in the search for new inhibitors of XO, as the activity of XO and hyperuricemia have also been associated with a variety of conditions such as diabetes, hypertension, and other cardiovascular diseases. In recent years the non-purine inhibitor febuxostat was approved in Europe and the USA for the treatment of hyperuricemia. This drug was followed by another XO inhibitor called topiroxostat. This review discusses the molecular structures and activities of the multiple classes of inhibitors that have been developed since the discovery of allopurinol, with a brief review of the molecular interactions between inhibitors and XO active site residues for the most important molecules. The challenges ahead for the discovery of new inhibitors of XO with novel chemical structures are discussed.

    Original languageEnglish
    Pages (from-to)714-743
    Number of pages30
    JournalChemMedChem
    Volume14
    Issue number7
    DOIs
    Publication statusPublished - 3 Apr 2019

    Keywords

    • drug design
    • hyperuricemia
    • inhibitors
    • purines
    • xanthine oxidase

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