Studies On The Screening Of Antibacterial Sensitizers For Flavonoids And Combined Antibacterial

With the increasing use of antibiotics and the serious shortage of new antibiotics,bacterial resistance has become one of the major threats to global health.Bacterial resistance has been a global public health event that will affect the development of modern medicine.Therefore,new strategies and new antibiotics are urgently needed to respond to bacterial resistance.Traditional antibiotics have been unable to meet the current treatment needs,and the rate of development of new antibacterial drugs has not kept up with the rate of occurrence of infectious diseases caused by pathogenic microorganisms.So,the indirect strategy is the focus of research.It is more effective to find antimicrobial sensitizers that can not only increase the antibacterial activity of antibiotics,but also reduce their use.In this study,the antibacterial activity of 12 flavonoids,12 isoflavones,and 12 chalcones were determined to screen out synergistic sensitizers in combination with cefuroxime sodium,azithromycin or ceftazidime.The minimal inhibitory concentration of the compound was measured by the microdilution method,and the antibacterial concentration of the single compound combined with the antibiotic was determined by the checkerboard dilution method.The sensitization effect was characterized by the bactericidal curve,combined drug sensitivity test paper method and the detection of bacterial migration ability.The results showed that 36 compounds showed certain activity against Staphylococcus aureus(ATCC 25923),Bacillus subtilis(ATCC 6633),Escherichia coli(ATCC 25922),and Pseudomonas aeruginosa(ATCC 15442),but the antibacterial activity of the compounds was weak.Among them,chrysin has a strong antibacterial activity.The structure of chrysin was analyzed.The antibacterial activity was found to be due to substitution of 5-and 7-positions in A ring with hydroxyl groups.B-rings and C-rings were formed without substituents.The antibacterial activity of isoflavone compounds is determined by the number of hydroxyl groups in the structure of the compound and the position of the substitution.In the chalcones structure,the hydroxyl group at the 4’ position of the A ring is critical to the bacteriostatic activity,and when it is replaced with methoxy and chlorine,the activity is reduced.If the B ring has no substituent,the antibacterial activity is stronger.When flavonoids,isoflavones,chalcones were combined with cefuroxime sodium or azithromycin,the combined use of antibacterial agents had different degrees of improvement.When the chalcone was combined with cefuroxime sodium or azithromycin,there was no synergistic effect on the four tested strains.The combination of a-napthaloflavone,diosmin or chrysin with cefuroxime sodium significantly enhanced Escherichia coli,Bacillus subtilis and Pseudomonas aeruginosa,and the antimicrobial inhibition rate ranged from 81%to 98%after combined use.The combination of B5,B8,B9,B10,B11,B12 with cefuroxime sodium also showed significant enhancement of Escherichia coli,Bacillus subtilis,and Pseudomonas aeruginosa,and the antimicrobial inhibition rate ranged from 78%to 98%after combined use.There was no synergistic effect when the single compound flavoxate hydrochloride,3-methylflavone-8-carboxylic acid and ceftazidime were combined.When combined with flavoxate hydrochloride and 3-methylflavone-8-carboxylic acid,combined with ceftazidime,the ability of the antibiotic to resist Staphylococcus aureus can be significantly enhanced with a synergistic effect.At the same time,the combination of the flavoxate hydrochloride and 3-methylflavone-8-carboxylic acid also can enhance the role of ceftazidime against Bacillus subtilis,Pseudomonas aeruginosa,Escherichia coli,Methicillin-resistant Staphylococcus aureus.