4-arylamidobenzyl substituted 5-bromomethylene-2(5 H )-furanones for chronic bacterial infection

Xu, Xingjun; Wang, Fang; Zeng, Ting; Lin, Jing; Chang, Yiqun; Sun, Ping‐Hua; Chen, Weimin

doi:10.1016/j.ejmech.2017.11.085

Cited by 15 publications

(6 citation statements)

References 49 publications

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“…Finally, Zn powder was found to be capable of reducing the double bonds of 5 under acidic conditions. 15,16 After preliminary screening (Table 1, entries 10−11), it was observed that the utilization of HCl resulted in a higher conversion compared to the use of AcOH. As such, a Zn powder/HCl system was chosen as the reducing agent for the subsequent steps.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Wu,

Guo,

Tang

et al. 2024

Org. Process Res. Dev.

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In the present study, a practical chemoenzymatic method was developed for the synthesis of chiral phenylalanine derivative 1, which is the key intermediate of Lifitegrast. In this established process, a simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromo-phenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. Then, the key chiral intermediate, 3-bromo-L-phenylalanine 7, could be obtained using acylase (ACY) AmACY. Upon process optimization, the chemical reaction was executed at a 300 g scale, with a notable substrate concentration reaching up to 100 g/L. The process achieved a yield of 40%, compared to a maximum theoretical yield of 50%, and exhibited an enantiomeric excess (ee) value reaching up to 99.9%. A simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromophenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. This synthetic pathway was effectively executed, yielding 1•HCl with a purity of 99.7% and an ee value of 99.9%, culminating in an overall yield of 23.4%. Additionally, the undesired (D)-6 enantiomer was recycled to form (rac)-6, employing an acetanhydride/acetic acid (Ac 2 O/AcOH) system. This recycling process achieved a yield of 47.5%, relative to a maximum theoretical yield of 50%, and a purity level of 99.8%.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Wu,

Guo,

Tang

et al. 2024

Org. Process Res. Dev.

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“…39 Halogenated furanone compounds are structurally similar to AHL and AI-2, so they combine with the receptors competitively, and finally inhibit the QS activity of various bacterial species. 40 More than 700 species of bacteria have been found in the human oral cavity, which establish mixed-species communities. 41 Studies have suggested that the microbiota in the peri-implant is a polymicrobial anaerobic infection.…”

Section: Discussionmentioning

confidence: 99%

Long-term antibacterial activity of a composite coating on titanium for dental implant application

et al. 2020

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Dental implants are the most innovative and superior treatment modality for tooth replacement. However, titanium implants still suffer from insufficient antibacterial capability and peri-implant diseases remain one of the most common and intractable complications. To prevent peri-implant diseases, a composite coating containing a new antibacterial agent, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF) was fabricated on titanium. This study was designed to investigate the antibacterial activity of the composite coating against two common peri-implant pathogens ( Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans). The morphology of the composite coating showed that BBF-loaded poly(L-lactic acid) nanospheres were well-distributed in the pores of the microarc oxidation coating, and cross-linked with each other and the wall pores by gelatin. A release study indicated that the antibacterial coating could sustain the release of BBF for 60 d, with a slight initial burst release occurring during the first 4 h. The antibacterial rate of the composite coating for adhering bacteria was the highest (over 97%) after 1 d and over 90% throughout a 30-day incubation period. The total fluorescence intensity of the composite coating was the lowest, and the vast majority of the fluorescence was red (dead bacteria). Moreover, real-time polymerase chain reaction analysis confirmed that the relative gene expression of the adherent bacteria on the composite coating was down-regulated. It was therefore concluded that the composite coating fabricated on titanium, which showed excellent and relatively long-term antibacterial activity against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, is a potential and promising strategy to be applied on dental implants for the prevention of peri-implant diseases.

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“…This combination of effects could be very useful in treating chronic infections, such as those found in wounds, where biofilm formation often causes a prolonged inflammatory state [87]. Xu et al (2018) showed that treatment with 10 µM rosiglitazone-furanone fusion inhibited QS by up to 50% across the Las, Rhl and PQS quorum sensing systems as shown by a reduction in fluorescence of PAO1 lasB-GFP, rhlA-GFP and pqsA-GFP reporter strains, respectively. In addition they observed a reduction in the pro-inflammatory cytokines Tissue Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6)in RAW264.7 murine macrophages, showing that the rosiglitazonefuranone compound simultaneously inhibited QS and achieved anti-inflammatory effects [88].…”

Section: Furanones As Potential Therapeuticsmentioning

confidence: 99%

“…Xu et al (2018) showed that treatment with 10 µM rosiglitazone-furanone fusion inhibited QS by up to 50% across the Las, Rhl and PQS quorum sensing systems as shown by a reduction in fluorescence of PAO1 lasB-GFP, rhlA-GFP and pqsA-GFP reporter strains, respectively. In addition they observed a reduction in the pro-inflammatory cytokines Tissue Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6)in RAW264.7 murine macrophages, showing that the rosiglitazonefuranone compound simultaneously inhibited QS and achieved anti-inflammatory effects [88]. Thus, while effective on their own, furanones have the potential to be combined with various other compounds to produce new, more effective therapies.…”

Section: Furanones As Potential Therapeuticsmentioning

confidence: 99%

Furanone quorum-sensing inhibitors with potential as novel therapeutics against Pseudomonas aeruginosa

Proctor

McCarron

Ternan

2020

Journal of Medical Microbiology

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Microorganisms use quorum sensing (QS), a cell density dependent process, to communicate. This QS mode of interchange leads to the production of a variety of virulence factors, coordination of complex bacterial behaviours, such as swarming motility, degradation of host tissue and biofilm formation. QS is implicated in numerous human infections and, consequently, researchers have sought ways of effectively inhibiting the process in pathogenic bacteria. Two decades ago, furanones were the first class of chemical compounds identified as Pseudomonas aeruginosa QS inhibitors (QSIs). P. aeruginosa is a ubiquitous organism, capable of causing a wide range of infections in humans, including eye and ear infections, wound infections and potentially fatal bacteraemia and thus novel treatments against this organism are greatly needed. This review provides a brief background on QS and the use of furanones as QSIs. Based on the effectiveness of action, both in vivo and in vitro, we will explore the use of furanones as potential antimicrobial therapeutics and conclude with open questions.

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4-arylamidobenzyl substituted 5-bromomethylene-2(5 H )-furanones for chronic bacterial infection

Cited by 15 publications

References 49 publications

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Long-term antibacterial activity of a composite coating on titanium for dental implant application

Furanone quorum-sensing inhibitors with potential as novel therapeutics against Pseudomonas aeruginosa

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