Natural Berberine-Hybridized Benzimidazoles as Novel Unique Bactericides against Staphylococcus aureus

Abstract

Natural berberine-hybridized benzimidazoles as potential antibacterial agents were constructed to treat Staphylococcus aureus infection in the livestock industry. Bioassay showed that some new berberine-benzimidazole hybrids exhibited potent antibacterial efficacies, especially, the 2,4-dichlorobenzyl derivative 7d not only showed strong activity against S. aureus ATCC 29213 with the MIC value of 0.006 mM but also effectively eradicated bacterial biofilm and exhibited low toxicity toward mammalian cells. The drug combination experiments showed that compound 7d together with norfloxacin could enhance the antibacterial efficacy. Moreover, the 2,4-dichlorobenzyl derivative 7d did not show obvious propensity to develop bacterial resistance. Preliminary mechanism studies revealed that the active molecule 7d could damage the membrane integrity, stimulate ROS generation, and bind with DNA as well as S. aureus sortase A, thus exerting powerful antibacterial ability. In light of these facts, berberine-benzimidazole hybrid 7d showed a large potentiality as a new bactericide for treating S. aureus in the livestock industry.

Unique Carbazole-Oxadiazole Derivatives as New Potential Antibiotics for Combating Gram-Positive and -Negative Bacteria

“…The outer membrane of Gram-negative bacteria is very challenging for small molecules to cross because small molecules are susceptible to efflux pumps when they are inside the cell. − To achieve a sufficient level, small molecules must possess the ability to effectively traverse porins to accumulate in Gram-negative bacteria. , Thus, docking simulations were conducted to investigate the binding of outer-membrane porins of P. aeruginosa with, respectively, compounds 5a , 5g , 5i – k , 13b – c , 16a – c , and 23b – c .…”

Natural Berberine-derived Azolyl Ethanols as New Structural Antibacterial Agents against Drug-Resistant Escherichia coli

“…The reaction mixture was reacted at room temperature for 3 h, and the precipitated solid was filtered. The residue was extracted with ethyl acetate (4 × 300 mL), and the collected organic solvent was evaporated to afford compound 1 in the yield of 69.9% without purification by silica gel chromatography. − The mixture of compound 1 (3.10 mmol), cesium carbonate (4.65 mmol). and tetrabutylammonium bromide (0.31 mmol) in acetonitrile (50 mL) was heated at 50 °C for 40 min.…”

A New Discovery of Unique 13-(Benzimidazolylmethyl)berberines as Promising Broad-Spectrum Antibacterial Agents

“…Recent studies revealed that the hybridization of berberine with heteroaromatics produced a variety of new structural berberine derivatives, some of which displayed satisfactory antibacterial activities and ideal pharmacokinetics. − Especially, our recent work demonstrated that the incorporation of benzimidazoles into the C-9 or C-12 position of berberine not only provided excellent antibacterial capacity and broad antimicrobial spectrum but also exhibited high biosafety and low drug resistance (Figure ). , Benzimidazole as a member of the recognized dominant heterocycle has been greatly favored in drug development because of its intrinsic feature of purine-resemblance structure, which capacitates its derivatives to hinder the biosynthesis of nucleic acid and proteins in the bacterial cell wall . The successful applications of commercial antimicrobial benzimidazole drugs like carbendazim and thiabendazole naturally stimulated extensive research in developing novel antibacterial structures on the basis of this fragment .…”