Glycosylated Flavonoids Have Fewer Antibacterial Activity than Corresponding Aglycone: Is It True for Antivirulence Activity?

Flavonoids are an important class of natural compounds with a broad spectrum of biological activities, which makes them interesting candidates for pharmaceutical applications. The current demand for novel compounds to control the bacterial infections has spurred a growing interest in antivirulence agents. Instead of inhibiting bacterial growth or killing pathogens, as classical antibacterials, these agents modulate bacterial virulence, disrupting the production or blocking virulence determinants that are essential for pathogenesis. Extensive research has been done on the structure–activity relationship of antibacterial glycosylated flavonoids and their respective aglycones. Glycosylation, particularly at the C-7 position of the main structure, is known to reduce the antibacterial activity of flavonoids. However, the impact of glycosylation on the antivirulence activity of flavonoids remains inadequately explored. This review addresses 54 glycosylated flavonoids and their effects on bacterial growth and virulence factors, including biofilms, motility, toxins, enzymes, pigments, and chemical communication systems. Although a relatively low number of correlation studies between the structure of flavonoids and antivirulence activities are available in literature, it is possible to infer that, in general, glycosylation negatively affects antivirulence property, similarly to what is documented for antibacterial activity. Sugar substituents at position C-7 have shown to also decrease antibiofilm action, and flavonoid neohesperidosides are more effective than rutinosides. Additionally, the position of glycosylation affects the antivirulence activity, especially in quorum sensing bacterial chemical communication system. However, synergistic effects of glycosylated flavonoids, especially flavanol-3-O-glycosides, with β-lactams and quinolones, are observed that suggest their potential use as adjuvants in antimicrobial therapy. The findings highlighted by this review are useful for the search, design, and development of new therapeutic alternatives to control bacterial infections.