Synthesis of Berberine and Canagliflozin Chimera and Investigation into New Antibacterial Activity and Mechanisms

Abstract

Berberine is an isoquinoline alkaloid isolated from Chinese herbal medicines such as Coptis chinensis. It has many pharmacological actions, such as antibacterial, hypoglycemic, anti-inflammatory, and so on. However, due to the low lipophilicity of berberine, it is difficult to penetrate the bacterial cell membrane and also difficult to be absorbed orally and usually needs a relatively high dose to achieve the ideal effect. The purpose of this study is to transform the structure of berberine in order to improve the bioavailability of berberine and reduce the dosage. Moreover, we introduce a pharmacophore named Canagliflozin, a hypoglycemic drug (which was also found to have potential anti-bacterial activity) into BBR to see whether this new compound has more existed activities. We at first connected berberine with Canagliflozin, to form a new compound (BC) and see whether BC has synergic effects. We use microbroth dilution method to determine the minimum inhibitory concentration of BC, determine the bacterial growth with the enzyme labeling instrument, observe the formation of bacterial biofilm with crystal violet staining method, observe the bacterial morphology with field emission scanning electron microscope, and determine the intracellular protein with SDS-PAGE. The above indicators reflect the damage of BC to bacteria. New compound BC was successfully obtained by chemical synthesis. The minimal inhibitory concentration of compound BC on three bacteria was significantly better than that of berberine and canagliflozin alone and the combination of berberine and canagliflozin. Moreover, compound BC has obvious destructive effect on bacterial morphology and biofilm, and the compound also has destructive effect on intracellular proteins. Therefore, new compound BC has broad-spectrum antibacterial activity and the inhibitory effect of BC might play a role by destroying the integrity of biofilm and the intracellular protein of bacteria. In conclusion, we create a new molecular entity of berberine and Canagliflozin chimera and open up a new prospect for berberine derivatives in the treatment of bacterial infection.

Antibacterial Activity and Mechanism of Canagliflozin against Methicillin-Resistant Staphylococcus aureus

“…Furthermore, canagliflozin and penicillin had strong additive antibacterial activity. Subsequent studies could consider chemical modifications or synthetic methods [36] to improve the antibacterial effects of canagliflozin. Canagliflozin holds potential research value in its antibacterial activity but requires further in vivo investigation into its exact molecular mechanisms and potential applications in the future.…”

Synthesis of New Derivatives of Berberine Canagliflozin and Study of Their Antibacterial Activity and Mechanism

“…Therefore, in our previous study, we synthesized a novel compound BC ( Figure 2 ) by chemically linking canagliflozin at the C13 position of berberine to enhance its hypoglycemic efficacy. Surprisingly, the results revealed that compound BC did not exhibit significant hypoglycemic activity; however, it displayed potent antibacterial properties against Pseudomonas aeruginosa [ 7 ]. Currently, approximately 700,000 individuals succumb to bacterial infections annually worldwide.…”

Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment

“…Berberine (BBR), a natural isoquinoline alkaloid, has many biological functions such as anti-inflammatory [ 32 ], anti-infection [ 33 ], and anti-arrhythmia [ 34 ] effects; diabetes treatment [ 35 ]; and the regulation of blood lipid and blood glucose. In particular, BBR has been developed as a first-line drug for the treatment of bacterial diarrhea [ 36 , 37 ]. BBR can inhibit DNA duplication, RNA transcription, protein biosynthesis, and enzyme activities and destroy the bacterial cell surface structure [ 38 ].…”