6-Bromo-2-Naphthol: RTP Enhancement and Synergy with Polymyxin

6-bromo-2-naphthol is a member of the class of naphthols that is 2-naphthol carrying an additional bromo substituent at position 6. It is a member of naphthols and an organobromine compound. It is functionally related to a 2-naphthol. 6-Bromo-2-naphthol is an RTP (Real-Time Polymerase Chain Reaction) probe that forms a 1:1 or 2:1 complex with β-cyclodextrin (β-CD). 6-Bromo-2-naphthol enables real-time monitoring of PCR reactions and quantification of specific nucleic acid sequences. 6-Bromo-2-naphthol is a class of small DNA or RNA sequences labeled with fluorescent dyes and bursting agents. RTP probes are a class of small DNA or RNA sequences labeled with fluorescent dyes and bursting agent molecules, and are widely used for gene expression analysis, SNP genotyping, and pathogen detection. 6-Bromo-2-naphthol is embedded in cyclodextrin cavities through hydrophobic interactions, inhibiting oxygen quenching effects, and emits a phosphorescent signal at room temperature. 6-Bromo-2-naphthol is also used as an intermediate in the synthesis of antimicrobial azodyes, whose derivatives are effective against many types of bacteria such as Staphylococcus aureus, E. coli, and other bacteria. Staphylococcus aureus, Escherichia coli and other bacteria.

6-bromo-2-naphthol in micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers

Room temperature phosphorescence (RTP) has been used as a selective and conventional analytical method for a wide range of organic and inorganic compounds. RTP has also been applied to elucidating kinetics of molecular dynamics in micellar systems. Since it is usually difficult to observe RTP in homogeneous solutions, various substrates have been employed for enhancing RTP. The substrates so far employed include conventional surfactant micelles, cyclodextrins, cellulose, silica, and their combined systems. Recently, polymer latex has proved to be a useful material for such purpose. In this study, we investigated RTP of 6-bromo-2-naphthol (BNL) in micelles of Pluronic L64 (L64) and Pluronic F68 (F68). The investigation was also directed toward RTP in the mixed aggregates of Pluronics with sodium dodecyl sulfate (SDS). RTP of 6-bromo-2-naphthol was enhanced to some extent in the micelles under deaerated condition, compared with that in aqueous homogeneous solutions where no RTP was detected. However, RTP was markedly enhanced in the mixed aggregates of Pluronic copolymers and SDS.[1]

6-Bromo-2-naphthol sensitizes Acinetobacter baumannii strains to polymyxin

Polymyxins are cationic amphipathic compounds that mainly kill gram-negative bacteria by selectively acting on lipid A of lipopolysaccharide (LPS), leading to increased membrane permeability and damaged cellular membranes. PMB-exposed cells are known to modify the phosphate of lipid A with phosphoethanolamine (PetN) or positively charged 4-amino-4-deoxy-l-arabinose, thereby increasing the bacterial surface charge, and reducing the binding of PMB to outer membranes.  In our study, the extracts obtained from Silene armeria, a plant species belonging to the family Caryophyllaceae were found to have a synergistic effect with PMB against A. baumannii. 6-Bromo-2-naphthol (6B2N) was identified as an effective compound to reduce the minimum inhibitory concentration (MIC) of PMB for killing A. baumannii. Our findings provide new directions for the effective control of MDR A. baumannii using a combination of PMB and natural extracts. Overnight cultured A. baumannii cells was diluted 1/100 in fresh LB broth, and 106 CFU/mL cells that reached the exponential phase were placed in 96-well plates. 6-bromo-2-naphthol was dissolved in EtOH and the concentration was set at 1–256 µg/mL. The FIC index was calculated using the same methods previously described.[2]

Q-TOF–LC/MS suggested that several candidate compounds (e.g., 6B2N, linoleic acid, piperochromeoic acid, and pregna-4,16-diene-3,11,20-trione) could be considered as adjuvants for potential combination therapy with PMB. Linoleic and oleic acids from H. pedunculatum are known to have antimicrobial activities against only gram-positive bacteria, including S. aureus. The synergistic concentration of 6-bromo-2-naphthol (16 μg/mL) was twofold lower than that of 1-naphthol (32 μg/mL), indicating that 6B2N dramatically affected the membranes of A. baumannii cells. 6B2N may contribute to. Our findings suggest that 6-bromo-2-naphthol from S. armeria can serve as a new synergistic compound for use with antibiotics by increasing cell membrane permeability and destabilizing the LPS layer of A. baumannii cells, thereby enhancing the effect of PMB.

References

[1]Nakashima K, Tango M, Araki K, Takeuchi K. Room temperature phosphorescence of 6-bromo-2-naphthol in micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers and in their mixed aggregates with sodium dodecyl sulfate. Spectrochim Acta A Mol Biomol Spectrosc. 2002 Jan 1;58(1):123-8. doi: 10.1016/s1386-1425(01)00523-6. PMID: 11808639.

[2]Kang M, Kim W, Lee J, Jung HS, Jeon CO, Park W. 6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin. Sci Rep. 2022 May 20;12(1):8546. doi: 10.1038/s41598-022-11995-y. PMID: 35595766; PMCID: PMC9123208.

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