Isoflavones, their Glycosides and Glycoconjugates. Synthesis and Biological Activity

Abstract

Glycosylation of small biologically active molecules, either of natural or synthetic origin, has a profound impact on their solubility, stability, and bioactivity, making glycoconjugates attractive compounds as therapeutic agents or nutraceuticals. A large proportion of secondary metabolites, including flavonoids, occur in plants as glycosides, which adds to the molecular diversity that is much valued in medicinal chemistry studies. The subsequent growing market demand for glycosidic natural products has fueled the development of various chemical and biotechnological methods of glycosides preparation. The review gives an extensive overview of the processes of the synthesis of isoflavones and discusses recently developed major routes towards isoflavone-sugar formation processes. Special attention is given to the derivatives of genistein, the main isoflavone recognized as a useful lead in several therapeutic categories, with particular focus on anticancer drug design. The utility of chemical glycosylations as well as glycoconjugates preparation is discussed in some theoretical as well as practical aspects. Since novel approaches to chemical glycosylations and glycoconjugations are abundant and many of them proved suitable for derivatization of polyphenols a new body of evidence has emerged, indicating that sugar moiety can play a much more significant role, when attached to a pharmacophore, then being a mere “solubilizer”. In many cases, it has been demonstrated that semisynthetic glycoconjugates are much more potent cytostatic and cytotoxic agents than reference isoflavones. Moreover, the newly designed glycosides or glycoside mimics can act through different mechanisms than the parent active molecule.

Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity

“…Natural polyphenolic compounds include of a wide variety of biologically active compounds, a number of which have been suggested to exhibit antineoplastic properties (40)(41)(42). However, the anti-cancer activity of patuletin has not yet been examined, to the best of our knowledge.…”

Enrichment of Polyglucosylated Isoflavones from Soybean Isoflavone Aglycones Using Optimized Amylosucrase Transglycosylation

“…The bioaccessibility of IFAs is low due to their poor solubility in water [7]. Therefore, various methods have been developed to overcome these shortcomings of IFAs [8,9].…”

Enhanced biotransformation of soybean isoflavone from glycosides to aglycones using solid‐state fermentation of soybean with effective microorganisms (EM) strains

“…Soybean [ Glycine max (L.) Merrill ], used as beneficial and nutritional dietary foods in several Asian countries, contains abundant soybean isoflavones (SIF) and has attracted great concerns due to their ability to inhibit cancer cell growth, to alleviate the symptoms of menopause and to prevent osteoporosis disease (Zaheer & Humayoun Akhtar, ). The biological effects of SIF are strongly influenced by their chemical structure (Szeja, Grynkiewicz, & Rusin, ). The β‐glycosidic forms are predominate in soybean, containing 50%–90% of isoflavones.…”