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Flavonoids are well known as antibacterial agents against a wide range of pathogenic microorganism. With increasing prevalence of untreatable infections induced by antibiotic resistance bacteria, flavonoids have attracted much interest because of the potential to be substitutes for antibiotics. In this review, the structure-relationship of flavonoids as antibacterial agents is summarized, and the recent advancements on the antibacterial mechanisms of flavonoids are also discussed. It is concluded that hydroxyls at special sites on the aromatic rings of flavonoids improve the activity. However, the methylation of the active hydroxyl groups generally decreases the activity. Besides, the lipopholicity of the ring A is vital for the activity of chalcones. The hydrophobic substituents such as prenyl groups, alkylamino chains, alkyl chains, and nitrogen or oxygen containing heterocyclic moieties usually enhance the activity for all the flavonoids. The proposed antibacterial mechanisms of flavonoids are as follows: inhibition of nucleic acid synthesis, inhibition of cytoplasmic membrane function, inhibition of energy metabolism, inhibition of the attachment and biofilm formation, inhibition of the porin on the cell membrane, alteration of the membrane permeability, and attenuation of the pathogenicity.

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