Structure–Activity Relationship of Flavonoids on Their Anti-Escherichia coli Activity and Inhibition of DNA Gyrase

Abstract

Flavonoids are potential sources of natural preservatives. The inhibitory activities of three polymethoxylated flavones (PMFs), three flavones, and four flavonols against Escherichia coli were determined using the microbroth dilution method. Flavonoid inhibitory activities against DNA gyrase from E. coli were estimated by DNA supercoiling. Kaempferol exhibited the greatest antibacterial activity [minimal inhibitory concentration (MIC) = 25 μg/mL], while nobiletin showed the lowest activity (MIC = 177 μg/mL). A good correlation was found between the pIC₅₀ values and the corresponding pMIC values for the purified DNA gyrase (r = 0.9582). The structure–activity relationship analysis suggests that, for a good inhibitory effect, the hydroxyl group substitution at C-5 in the A ring and C-4′ in the B ring and the methoxyl group substitution at C-3 and C-8 in the A ring are essential. The presence of the hydroxyl group at C-6 in the A ring, C-3′ and C-5′ in the B ring, and C-3 in the C ring and the methoxyl group at C-3′ in the B ring greatly reduced inhibition of bacteria. These findings provide a theoretical basis for the development of high-bioactive and low-toxicity natural preservatives.