Valentina Straniero (Author), Victor Sebastián-Pérez (Author), Lorenzo Suigo (Author), William Margolin (Author), Andrea Casiraghi (Author), Martina Hrast (Author), Carlo Zanotto (Author), Irena Zdovc (Author), Antonia Radaelli (Author), Ermanno Valoti (Author)

Abstract

Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This resistant strain is associated with a 64% increase in death compared to the antibiotic-susceptible strain. The prokaryotic protein FtsZ and the cell division cycle have been validated as potential targets to exploit in the general battle against antibiotic resistance. Despite the discovery and development of several anti-FtsZ compounds, no FtsZ inhibitors are currently used in therapy. This work further develops benzodioxane-benzamide FtsZ inhibitors. We seek to find more potent compounds using computational studies, with encouraging predicted drug-like profiles. We report the synthesis and the characterization of novel promising derivatives that exhibit very low MICs towards both methicillin-susceptible and -resistant S. aureus, as well as another Gram positive species, Bacillus subtilis, while possessing good predicted physical-chemical properties in terms of solubility, permeability, and chemical and physical stability. In addition, we demonstrate by fluorescence microscopy that Z ring formation and FtsZ localization are strongly perturbed by our derivatives, thus validating the target.

Keywords

Veterinarska medicina;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL VF - Veterinary Faculty
UDC: 579:615.2:57.08
COBISS: 59812611 Link will open in a new window
ISSN: 2079-6382
Views: 177
Downloads: 40
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Other data

Secondary language: Slovenian
Secondary keywords: Anti-Bacterial Agents;Pharmacology;Chemistry;Methicillin-Resistant Staphylococcus aureus;Bacillus subtilis;Drug resistance, microbial;Benzamides;Bacterial proteins;
Type (COBISS): Article
Pages: art. 442, str. 1-19
Volume: ǂVol. ǂ10
Issue: ǂno. ǂ4
Chronology: 2021
DOI: 10.3390/antibiotics10040442
ID: 14704359