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Molecules 2016, 21(2), 241; doi: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

Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, I-90123 Palermo, Italy
IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Emerico Amari 123, I-90139 Palermo, Italy
Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, 1067 Riga, Latvia
Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Viale A. Doria 6 Ed. 2, Città Universitaria, I-95125 Catania, Italy
Authors to whom correspondence should be addressed.
Academic Editor: Peter J. Rutledge
Received: 26 December 2015 / Revised: 5 February 2016 / Accepted: 12 February 2016 / Published: 19 February 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [923 KB, uploaded 19 February 2016]   |  


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. View Full-Text
Keywords: sortase A; biofilms; 2-(2-phenylhydrazinylidene)alkanoic acid derivatives; FRET sortase A; biofilms; 2-(2-phenylhydrazinylidene)alkanoic acid derivatives; FRET

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Maggio, B.; Raffa, D.; Raimondi, M.V.; Cascioferro, S.; Plescia, F.; Schillaci, D.; Cusimano, M.G.; Leonchiks, A.; Zhulenkovs, D.; Basile, L.; Daidone, G. Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-Positive Pathogens: 2-(2-Phenylhydrazinylidene)alkanoic Acids and Related Derivatives. Molecules 2016, 21, 241.

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