2020
DOI: 10.3389/fmicb.2020.560798
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A Novel Promazine Derivative Shows High in vitro and in vivo Antimicrobial Activity Against Staphylococcus aureus

Abstract: The emergence of multidrug-resistant bacteria constitutes a significant public health issue worldwide. Consequently, there is an urgent clinical need for novel treatment solutions. It has been shown in vitro that phenothiazines can act as adjuvants to antibiotics whereby the minimum inhibitory concentration (MIC) of the antibiotic is decreased. However, phenothiazines do not perform well in vivo, most likely because they can permeate the blood-brain (BBB) barrier and cause severe side-effects to the central ne… Show more

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Cited by 9 publications
(16 citation statements)
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“…In this study, the MIC for JBC 1847 was found to be 1 mg/L whereas the MIC for promazine previously has been determined to be 128 mg/L in S. aureus JE2 (Jørgensen, 2020) and in other strains of S. aureus (Nehme et al, 2018). Furthermore, JBC 1847 is not acting synergistically with oxacillin whereas this property has been reported for various phenothiazines (Klitgaard et al, 2008;Hadji-Nejad et al, 2010) and previously we have shown via in silico analysis that JBC 1847 exhibits different pharmacological parameters than promazine (Ronco et al, 2020(Ronco et al, , 2021a. In contrast to promazine, the transcriptomic profile of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 is highly similar to transcriptomic profile of S. aureus exposed to sub-inhibitory concentrations of T5, another phenothiazine [thioridazine (10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfanylphenothiazine) (Wassmann et al, 2018)] derivative (Jørgensen et al, 2020).…”
Section: Discussionmentioning
confidence: 71%
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“…In this study, the MIC for JBC 1847 was found to be 1 mg/L whereas the MIC for promazine previously has been determined to be 128 mg/L in S. aureus JE2 (Jørgensen, 2020) and in other strains of S. aureus (Nehme et al, 2018). Furthermore, JBC 1847 is not acting synergistically with oxacillin whereas this property has been reported for various phenothiazines (Klitgaard et al, 2008;Hadji-Nejad et al, 2010) and previously we have shown via in silico analysis that JBC 1847 exhibits different pharmacological parameters than promazine (Ronco et al, 2020(Ronco et al, , 2021a. In contrast to promazine, the transcriptomic profile of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 is highly similar to transcriptomic profile of S. aureus exposed to sub-inhibitory concentrations of T5, another phenothiazine [thioridazine (10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfanylphenothiazine) (Wassmann et al, 2018)] derivative (Jørgensen et al, 2020).…”
Section: Discussionmentioning
confidence: 71%
“…The antimicrobial compounds JBC 1847 and T5 (molecular structures are presented in Supplementary Figure 1 ) were synthesized at University of Copenhagen, Denmark, as previously reported ( Jørgensen et al, 2020 ; Ronco et al, 2020 ). All other antimicrobials were purchased at Sigma-Aldrich (Brøndby, Denmark), unless mentioned otherwise.…”
Section: Methodsmentioning
confidence: 99%
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