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GIUSEPPE DAIDONE

Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and related derivatives

  • Autori: Maggio, B.; Raffa, D.; Raimondi, M.; Cascioferro, S.; Plescia, F.; Schillaci, D.; Cusimano, M.; Leonchiks, A.; Zhulenkovs, D.; Basile, L.; Daidone, G.
  • Anno di pubblicazione: 2016
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: 2-(2-phenylhydrazinylidene)alkanoic acid derivatives; Biofilms; FRET; Sortase A; Organic Chemistry

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.

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