Flavonoids: A Review of Antibacterial Activity Against Gram-Negative Bacteria

The rise in bacterial resistance to conventional antibiotics has led to the search for alternative antimicrobial agents, such as flavonoids, which are widely distributed in plants and known for their antibacterial properties. This review examines the antibacterial activity of flavonoids against Gram-negative bacteria and identifies gaps in current knowledge. The analysis of available data revealed that several flavonoids, such as liricidin-7-O-hexoside, licoflavone C, and dorsmanins C and F, demonstrated remarkable antibacterial potential. It was also observed that flavonoids exhibit multifactorial antibacterial activity, interfering with various cellular bacterial processes such as maintaining cell membrane integrity, energy metabolism, and protein synthesis. However, despite the growing number of studies indicating the promising potential of these compounds against bacterial pathogens, many of these studies mainly focus on in vivo evaluations, limited to verifying the presence or absence of antibacterial activity, without an in-depth investigation of the mechanisms of action or clinical efficacy of flavonoids. Additionally, most research has been conducted on a limited number of bacterial species, such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Furthermore, few studies have explored the effects of pure flavonoids, as most investigations have centered on extracts or flavonoid-rich fractions. There is a significant gap in research regarding the antibacterial activity of isolated flavonoids against Gram-negative bacteria. The review calls for further studies on pure flavonoids, focusing on understanding their mechanisms of action, interactions with other therapies, pharmacokinetics, toxicity, and clinical effectiveness to develop more targeted treatments for multidrug-resistant bacterial infections.