A structure–activity relationship study of flavonoids as inhibitors of E. coli by membrane interaction effect

Abstract

Flavonoids exhibit a broad range of biological activities including antibacterial activity. However, the mechanism of their antibacterial activity has not been fully investigated. The antibacterial activity and membrane interaction of 11 flavonoids (including 2 polymethoxyflavones and 4 isoflavonoids) against Escherichia coli were examined in this study. The antibacterial capacity was determined as flavonoids>polymethoxyflavones>isoflavonoids. Using fluorescence, it was observed that the 5 flavonoids rigidified the liposomal membrane, while the polymethoxyflavones and isoflavonoids increased membrane fluidity. There was a significant positive correlation between antibacterial capacity and membrane rigidification effect of the flavonoids. A quantitative structure-activity relationship (QSAR) study demonstrated that the activity of the flavonoid compounds can be related to molecular hydrophobicity (CLogP) and charges on C atom at position3 (C3). The QSAR model could be used to predict the antibacterial activity of flavonoids which could lead to natural compounds having important use in food and medical industry.

Antibacterial evaluation of flavonoid compounds against E. coli by microcalorimetry and chemometrics

“…This indicated that the type of substituent group at position 4′ in the B ring is crucial to the antibacterial effects of the two flavonoid compounds. There are four additional free hydroxyls in the glucoside of liquiritin which might be the key factor in inducing the antibacterial effect, indicating that the introduction of hydroxyl group at position 4′ in the B ring enhances the antibacterial effects of flavonoid compounds, which is in agreement with previous reports (Alcaráz et al 2000;Sato et al 1997;Tim Cushnie and Lamb 2005;Wu et al 2013). …”

“…Using this microcalorimetric method, some critical information including the real-time metabolic power-time curve together with quite a few quantitative thermokinetic parameters of E. coli growth in the presence of the test compounds was obtained. This was previously not possible by traditional microbiological methods including the agar cup method and the serial dilution method (Alcaráz et al 2000;Dastidar et al 2004;Liu et al 2000;Tim Cushnie and Lamb 2005;Wu et al 2013) but was very crucial in the antibacterial assessment (Ferreira et al 2015;Guo et al 2012;Kong et al 2012). Combined with chemometric approaches, such as SA, MANOVA, and PCA, the antibacterial effects of the two flavonoid compounds on E. coli were quickly and systematically evaluated.…”

“…Consequently, the increasingly documented antibacterial effects of flavonoid compounds are determined to a certain extent by their structural properties, especially the number, types, and positions of some substituent groups, such as methoxyl and hydroxyl groups (Ohemeng et al 1993;Tim Cushnie and Lamb 2005;Wu et al 2013;Zhong et al 2011). Structurally, the flavonoids are derived from the parent compound exhibiting a diphenylpropane (C6-C3-C6) skeleton (Fig.…”

“…Increasing numbers of studies have used various assays to assess the antibacterial effects of flavonoids, such as the agar dilution technique, the paper disk diffusion assay, the cylinder diffusion method, the broth macrodilution technique, and the broth microdilution technique (Alcaráz et al 2000;Dastidar et al 2004;Liu et al 2000;Wu et al 2013). However, sometimes the results obtained by different methods cause confusion or inconsistencies.…”

ASSESSMENT OF BIOACTIVE METABOLITES FROM THE ROOT ENDOPHYTE ISOLATED FROM CASUARINA JUNGHUHNIANA Miq.

“…The number of phenolic groups may attribute to their relative toxicity to microorganism because of increase in hydroxylation causing greater toxicity [37]. The difference in the antibacterial activity can be attributed to the class of flavonoids (flavones, flavonols, flavan-3-ols, isoflavones, flavanones, and anthocyanidins) and/ or their chemical structure, specifically in regards to the position and number of methoxy and phenolic group within their structure [38][39][40].…”