Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens

Gómez, Andromeda-Celeste; Lyons, Thérèse; Mamat, Uwe; Yero, Daniel; Bravo, Marc; Daura, Xavier; Elshafee, Osama; Brunke, Sascha; Gahan, Cormac G. M.; O’Driscoll, Michelle; Gibert, Isidre; O’Sullivan, Timothy P.

doi:10.1016/j.ejmech.2022.114678

Cited by 14 publications

(11 citation statements)

References 65 publications

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“…In addition, several volatile compounds were found in the SPE, of which furanone is the most predominant. Interestingly, a previous study evidenced the biological activity of furanone against some germs [46]. Similarly, several studies reported that a large number of halogenated furanones and related synthetic analogues, were later discovered to inhibit the biofilm formation in a variety of pathogens [47][48][49].…”

Section: Discussionmentioning

confidence: 96%

Chemical Composition Profiling and Antifungal Activity of Saffron Petal Extract

et al. 2022

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Numerous fungal plant pathogens can infect fresh fruits and vegetables during transit and storage conditions. The resulting infections were mainly controlled by synthetic fungicides, but their application has many drawbacks associated with the threatened environment and human health. Therefore, the use of natural plants with antimicrobial potential could be a promising alternative to overcome the side effects of fungicides. In this regard, this study aimed at evaluating the antifungal activity potential of saffron petal extract (SPE) against three mains important fungal pathogens: Rhizopus stolonifer, Penicillium digitatum and Botritys cinerea, which cause rot decay on the tomato, orange and apple fruits, respectively. In addition, the organic composition of SPE was characterized by attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and its biochemical, and gas chromatography-mass spectrometry (GC-MS) analyses were carried out. The obtained results highlighted an increased inhibition rate of the mycelial growth and spore germination of the three pathogenic fungi with increasing SPE concentrations. The mycelial growth and spore germination were completely inhibited at 10% of the SPE for Rhizopus stolonifer and Penicillium digitatum and at 5% for B. cinerea. Interestingly, the in vivo test showed the complete suppression of Rhizopus rot by the SPE at 10%, and a significant reduction of the severity of grey mold disease (37.19%) and green mold, when applied at 5 and 10%, respectively. The FT-IR spectra showed characteristic peaks and a variety of functional groups, which confirmed that SPE contains phenolic and flavonoid components. In addition, The average value of the total phenolic content, flavonoid content and half-maximal inhibitory concentration (IC50) were 3.09 ± 0.012 mg GAE/g DW, 0.92 ± 0.004 mg QE/g DW and 235.15 ± 2.12 µg/mL, respectively. A volatile analysis showed that the most dominant component in the saffron petal is 2(5H)-Furanone (92.10%). Taken together, it was concluded that SPE could be used as an alternative to antioxidant and antifungal compounds for the control of postharvest diseases in fruits.

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Section: Discussionmentioning

confidence: 96%

Chemical Composition Profiling and Antifungal Activity of Saffron Petal Extract

et al. 2022

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“…Other halogen-containing polyphenols, especially brominated furanones, have also been identified as having anti-biofilm properties for Gram-positive and Gram-negative bacteria, including Staphylococci. The proposed mechanism of action for these furanones is as quorum-sensing inhibitors [ 70 , 71 , 72 , 73 , 74 , 75 ]. Although the AT compounds no longer contain the aurone furan ring, the AT ring structures are halogenated with both AT125 and AT137 having a bromine either on the salicyl or the thiophene ring.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Antibacterial Effect of Aurone-Derived Triazoles on Staphylococcus aureus

Szepe,

Kafle,

Bhattarai

et al. 2023

Antibiotics

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Infections caused by antibiotic-resistant bacteria continue to pose a significant public health threat despite their overall decreasing numbers in the last two decades. One group of compounds fundamental to the search for new agents is low-cost natural products. In this study, we explored a group of newly synthesized novel aurone-derived triazole compounds to identify those with pharmaceutical potential as inhibitors of antibiotic-resistant Staphylococcus aureus. Using the broth microdilution method, antibacterial activities against methicillin-resistant S. aureus ATCC 43300 (MRSA) and methicillin-sensitive S. aureus ATCC 29213 (MSSA) were identified for four aurone-derived triazole compounds, AT106, AT116, AT125, and AT137, using the half-maximal inhibitory concentrations for the bacteria (IC50) and mammalian cell lines (CC50). Compounds AT125 and AT137 were identified to have pharmaceutical potential as the IC50 values against MRSA were 5.412 µM and 3.870 µM, whereas the CC50 values measured on HepG2 cells were 50.57 µM and 39.81 µM, respectively, resulting in selectivity indexes (SI) > 10. Compounds AT106 and AT116 were also selected for further study. IC50 values for these compounds were 5.439 µM and 3.178 µM, and the CC50 values were 60.33 µM and 50.87 µM, respectively; however, SI values > 10 were for MSSA only. Furthermore, none of the selected compounds showed significant hemolytic activity for human erythrocytes. We also tested the four compounds against S. aureus biofilms. Although AT116 and AT125 successfully disrupted MSSA biofilms, there was no measurable potency against MRSA biofilms. Checkerboard antibiotic assays to identify inhibitory mechanisms for these compounds indicated activity against bacterial cell membranes and cell walls, supporting the pharmaceutical potential for aurone-derived triazoles against antibiotic-resistant bacteria. Examining structure–activity relationships between the four compounds in this study and other aurone-derived triazoles in our library suggest that substitution with a halogen on either the salicyl ring or triazole aryl group along with triazoles having nitrile groups improves anti-Staphylococcal activity with the location of the functionality being very important.

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“…This is achieved while safeguarding beneficial, commensal microbiota without compromising the bacterial viability. These anti-virulence drugs are further classified into various groups, including adhesion and attachment inhibitors, toxin inhibitors, secretion inhibitors, communication and signaling inhibitors, among others ( Ogawara, 2021 ; Gómez et al., 2022 ). Many virulence factors are involved in bacterial biofilm formation.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of novel compounds as anti-bacterial or anti-virulence agents

Filipić,

Ušjak,

Rambaher

et al. 2024

Front. Cell. Infect. Microbiol.

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Antimicrobial resistance is a global threat, leading to an alarming increase in the prevalence of bacterial infections that can no longer be treated with available antibiotics. The World Health Organization estimates that by 2050 up to 10 million deaths per year could be associated with antimicrobial resistance, which would equal the annual number of cancer deaths worldwide. To overcome this emerging crisis, novel anti-bacterial compounds are urgently needed. There are two possible approaches in the fight against bacterial infections: a) targeting structures within bacterial cells, similar to existing antibiotics; and/or b) targeting virulence factors rather than bacterial growth. Here, for the first time, we provide a comprehensive overview of the key steps in the evaluation of potential new anti-bacterial and/or anti-virulence compounds. The methods described in this review include: a) in silico methods for the evaluation of novel compounds; b) anti-bacterial assays (MIC, MBC, Time-kill); b) anti-virulence assays (anti-biofilm, anti-quorum sensing, anti-adhesion); and c) evaluation of safety aspects (cytotoxicity assay and Ames test). Overall, we provide a detailed description of the methods that are an essential tool for chemists, computational chemists, microbiologists, and toxicologists in the evaluation of potential novel antimicrobial compounds. These methods are cost-effective and have high predictive value. They are widely used in preclinical studies to identify new molecular candidates, for further investigation in animal and human trials.

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Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens

Cited by 14 publications

References 65 publications

Chemical Composition Profiling and Antifungal Activity of Saffron Petal Extract

Chemical Composition Profiling and Antifungal Activity of Saffron Petal Extract

Evaluation of the Antibacterial Effect of Aurone-Derived Triazoles on Staphylococcus aureus

Evaluation of novel compounds as anti-bacterial or anti-virulence agents

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