ABSTRACT
Antimicrobial resistance (AMR) poses a serious threat to human health, and new antimicrobial agents are desperately needed. Plant flavonoids are increasingly being paid attention to for their antibacterial activities, for the enhancing of the antibacterial activity of antimicrobials, and for the reversing of AMR. To obtain more scientific and reliable equations, another two regression equations, between the minimum inhibitory concentration (MIC) (y) and the lipophilicity parameter ACD/LogP or LogD7.40 (x), were established once again, based on the reported data. Using statistical methods, the best one of the four regression equations, including the two previously reported, with regard to the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria, is y = -0.1285 x6 + 0.7944 x5 + 51.785 x4 - 947.64 x3 + 6638.7 x2 - 21,273 x + 26,087; here, x is the LogP value. From this equation, the MICs of most plant flavonoids to Gram-positive bacteria can be calculated, and the minimum MIC was predicted as approximately 0.9644 µM and was probably from 0.24 to 0.96 µM. This more reliable equation further proved that the lipophilicity is a key factor of plant flavonoids against Gram-positive bacteria; this was further confirmed by the more intuitive evidence subsequently provided. Based on the antibacterial mechanism proposed in our previous work, these also confirmed the antibacterial mechanism: the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, and this involves the damage of the phospholipid bilayers. The above will greatly accelerate the discovery and application of plant flavonoids with remarkable antibacterial activity and the thorough research on their antimicrobial mechanism.
ABSTRACT
Antimicrobial resistance seriously threatened human health, and new antimicrobial agents are desperately needed. As one of the largest classes of plant secondary metabolite, flavonoids can be widely found in various parts of the plant, and their antibacterial activities have been increasingly paid attention to. Based on the physicochemical parameters and antibacterial activities of sixty-six flavonoids reported, two regression equations between their ACD/LogP or LogD7.40 and their minimum inhibitory concentrations (MICs) to gram-positive bacteria were established with the correlation coefficients above 0.93, and then were verified by another sixty-eight flavonoids reported. From these two equations, the MICs of most flavonoids against gram-positive bacteria could be roughly calculated from their ACD/LogP or LogD7.40, and the minimum MIC was predicted as approximately 10.2 or 4.8 µM, more likely falls into the range from 2.6 to 10.2 µM, or from 1.2 to 4.8 µM. Simultaneously, both tendentiously concave regression curves indicated that the lipophilicity is a key factor for flavonoids against gram-positive bacteria. Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.