Structure-Activity and Lipophilicity Relationships of Selected Antibacterial Natural Flavones and Flavanones of Chilean Flora

Abstract

In this study, we tested eight naturally-occurring flavonoids—three flavanones and five flavones—for their possible antibacterial properties against four Gram-positive and four Gram-negative bacteria. Flavonoids are known for their antimicrobial properties, and due their structural diversity; these plant-derived compounds are a good model to study potential novel antibacterial mechanisms. The lipophilicity and the interaction of antibacterial compounds with the cell membrane define the success or failure to access its target. Therefore, through the determination of partition coefficients in a non-polar/aqueous phase, lipophilicity estimation and the quantification of the antibacterial activity of different flavonoids, flavanones, and flavones, a relationship between these parameters was assessed. Active flavonoids presented diffusion coefficients between 9.4 × 10−10 and 12.3 × 10−10 m2/s and lipophilicity range between 2.0 to 3.3. Active flavonoids against Gram-negative bacteria showed a narrower range of lipophilicity values, compared to active flavonoids against Gram-positive bacteria, which showed a wide range of lipophilicity and cell lysis. Galangin was the most active flavonoid, whose structural features are the presence of two hydroxyl groups located strategically on ring A and the absence of polar groups on ring B. Methylation of one hydroxyl group decreases the activity in 3-O-methylgalangin, and methylation of both hydroxyl groups caused inactivation, as shown for 3,7-O-dimethylgalangin. In conclusion, the amphipathic features of flavonoids play a crucial role in the antibacterial activity. In these compounds, hydrophilic and hydrophobic moieties must be present and could be predicted by lipophilicity analysis.

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

“…Interestingly, the presence of hydroxyl groups in the phenyl rings A and B did not influence their activity, with the exception of Staphylococcus aureus [91]. On the contrary, Echeverría et al [92] reported that methylation of one hydroxyl group decreased the activity in 3-O-methylgalangin, and methylation of both hydroxyl groups caused inactivation against Bacillus subtilis and Escherichia coli. These findings highlight the importance of the structure-activity relationship when considering the antibacterial potential of natural compounds.…”

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

“…The relationship between lipophilicity and the structure of flavonoid analogues in growth inhibition of Gram‐positive and Gram‐negative bacteria were evaluated by flavones from Heliotropium filifolium . Compounds pinocembrin ( 87 ) and 7‐O‐methyleriodictyol ( 99 ) were active with MIC values of 0.5–4 μg/ml, and these results showed that the amphipathic properties (lipophilic and hydrophilic moieties of flavones) were important for antibacterial activity and selectivity, respectively (Echeverría et al, ).…”

“…The amphipathic features of flavonoids play an important role in the antibacterial properties. In these compounds, hydrophilic and hydrophobic moieties must be present together (Echeverría et al, ). The hydrophobic substituents such as prenyl groups, alkylamino chains, alkyl chains, and nitrogen or oxygen containing heterocyclic moieties usually enhance the antibacterial activity for all the flavonoids (Xie, Yang, Tang, Chen, & Ren, ).…”

“…For example, comparison of compounds with the same structure showed that kaempferol ( 55 ) with a hydroxy group at C‐4′ had less activity than galangin ( 44 ; without OH at C‐4′) against S . aureus (Echeverría et al, ).…”

Antibacterial Activity Against Bacillus Subtilis and Antioxidant Properties of Methanol Extracts From Garcinia Latissima Miq. Leaves

“…The relationship between antibacterial activity and contents of active compounds in plant extracts or fractions of G. latissima have been investigated in multiple previous studies [1,[17][18][19][20][21]. Moreover, phytochemical tests of methanol extracts of G. latissima leaves showed the presence of tannin and saponin, which are known phytochemicals with health benefits and biological activities [4].…”