Abstract
A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 µM.
Highlights
Antibiotic resistance is a very important challenge and in 2015 the World Health Organization (WHO) considered it as one of the most important global health problems [1]
An Considering anti-virulencethat strategy based on agents target virulencepathogenesis determinants could be effective in is bacterial adhesion, promoted by of theGram surface exposed proteins at the cell wall, we presume preventing the biofilm formation positive bacteria that are naturally resistant to currentthat
It is well established that the above class of derivatives exist in the arylhydrazinylidene The reported synthetic method was further modified, and the abovementioned esters 1a–d,f,g, and form [23,24], one needs to assign the geometrical structure of the substituted compound 7a were obtained
Summary
Antibiotic resistance is a very important challenge and in 2015 the World Health Organization (WHO) considered it as one of the most important global health problems [1]. SrtA mutant strains are less virulent than wild strains and they are defective during their pathogenic (FnbpA and FnbpB) and two clumping factors (ClfA and ClfB) Some of these proteins play key roles action [7]. An Considering anti-virulencethat strategy based on agents target virulencepathogenesis determinants could be effective in is bacterial adhesion, promoted by of theGram surface exposed proteins at the cell wall, we presume preventing the biofilm formation positive bacteria that are naturally resistant to currentthat. A number of promising small synthetic organic compounds that work as effective SrtA inhibitors of classes of described inhibitors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
