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.

Maggio, B., Raffa, D., Raimondi, M., Cascioferro, S., Plescia, F., Schillaci, D., et al. (2016). Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and related derivatives. MOLECULES, 21(2), 1-14 [10.3390/molecules21020241].

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

MAGGIO, Benedetta
;
RAFFA, Demetrio
;
RAIMONDI, Maria Valeria;CASCIOFERRO, Stella Maria;PLESCIA, Fabiana;SCHILLACI, Domenico;CUSIMANO, Maria Grazia;BASILE, Livia;DAIDONE, Giuseppe
2016-02-19

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.
19-feb-2016
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/19 - Microbiologia Generale
Maggio, B., Raffa, D., Raimondi, M., Cascioferro, S., Plescia, F., Schillaci, D., et al. (2016). Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and related derivatives. MOLECULES, 21(2), 1-14 [10.3390/molecules21020241].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/179975
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