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The emergence of pathogenic multidrug-resistant bacteria demands new approaches in finding effective antibacterial agents. Synthetic flavonoids could be a reliable solution due to their important antimicrobial activity. We report here the potent  in vitro  antibacterial activity of  ClCl-flav —a novel synthetic tricyclic flavonoid. The antimicrobial effects were tested using the minimum inhibitory concentration (MIC), time kill and biofilm formation assays. Fluorescence microscopy and scanning electron microscopy were employed to study the mechanism of action. MTT test was used to assess the cytotoxicity of  ClCl-flav . Our results showed that Gram positive bacteria were more sensitive (MIC = 0.24 μg/mL) to  ClCl-flav  compared to the Gram negative ones (MIC = 3.9 μg/mL). We found that our compound showed significantly enhanced antibacterial activities, 32 to 72-fold more active than other synthetic flavonoids.  ClCl-flav  showed bactericidal activity at concentrations ranging from 0.48 to 15.62 μg/mL. At twice the MIC, all  Escherichia coli  and  Klebsiella pneumoniae  cells were killed within 1 h. Also  ClCl-flav  presented good anti-biofilm activity. The mechanism of action is related to the impairment of the cell membrane integrity. No or very low cytotoxicity was evidenced at effective concentrations against Vero cells. Based on the strong antibacterial activity and cytotoxicity assessment,  ClCl-flav  has a good potential for the design of new antimicrobial agents.

A novel synthetic flavonoid with potent antibacterial properties: In vitro activity and proposed mode of action