Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-Positive Pathogens: 2-(2-Phenylhydrazinylidene)alkanoic Acids and Related Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2016 Feb 25

PMID 26907235

Citations 12

Authors

Benedetta Maggio

Demetrio Raffa

Maria Valeria Raimondi

Stella Cascioferro

Fabiana Plescia

Domenico Schillaci

Maria Grazia Cusimano

Ainars Leonchiks

Dmitrijs Zhulenkovs

Livia Basile

Giuseppe Daidone

Affiliations

Soon will be listed here.

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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