Sulfated flavonoids: An updated and comprehensive review of their chemistry and bioactivities

Sulfated flavonoids, also named flavonoid sulfates, are a class of polyphenol derivatives from various plants often with a long history of use in traditional medicine around the world, that play an important role in secondary metabolism, chemical defense, and growth regulation of plants, and with significant and potential health benefits. Sulfated flavonoids are produced by a substitution reaction of a flavonoid moiety and a sulfate donor, where transfer of a sulfate group to hydroxyl groups in the flavonoid structure is catalyzed, either naturally or synthetically, by the enzyme sulfotransferase. Of note, several monocotyledonous and dicotyledonous plant families have been reported for their content of sulfated flavonoids. Various medically important bioactivities have been reported for sulfated flavonoids, including antitumor, antidiabetic, antimicrobial, and antiviral properties, and which we discuss in this review. The present review focuses on sulfated flavonoids extracted from plants but also discuss some chemically synthesized sulfated flavonoids explored, e.g., for their (potential) anticoagulant properties. This review aims to summarize the published data on naturally occurring and synthetic sulfated flavonoids, paying particular attention to their structural variations and occurrence, biosynthesis aspects, methods of identification, extraction and isolation, and biological activities. The review covers literature published in English, spanning the entire period from the first report in 1971 to January 2025. Finally, the current work emphasizes this class of compounds as a source of potential candidates for the development of new pharmaceutical drugs with beneficial bioactivities.