English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 nervous system. Therefore, the aim of this study was to synthesize a promazine derivate that would not cross the BBB but retain its properties as antimicrobial helper compound. Surprisingly,  in vitro  studies showed that the novel compound, JBC 1847 exhibited highly increased antimicrobial activity against eight Gram-positive pathogens (MIC, 0.5–2 mg/L), whereas a disc diffusion assay indicated that the properties as an adjuvant were lost. JBC 1847 showed significant ( P  < 0.0001) activity against a  Staphylococcus aureus  strain compared with the vehicle, in an  in vivo  wound infection model. However, both  in vitro  and  in silico  analyses showed that JBC 1847 possesses strong affinity for human plasma proteins and an Ames test showed that generally, it is a non-mutagenic compound. Finally,  in silico  predictions suggested that the compound was not prone to pass the BBB and had a suitable permeability to the skin. In conclusion, JBC 1847 is therefore suggested to hold potential as a novel topical agent for the clinical treatment of  S. aureus  skin and soft tissue infections, but pharmacokinetics and pharmacodynamics need to be further investigated.

A Novel Promazine Derivative Shows High in vitro and in vivo Antimicrobial Activity Against Staphylococcus aureus