Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents

Antibacterial Agents; Bacteria; Chemistry Techniques, Synthetic; Chromatography, High Pressure Liquid; Chromatography, Liquid; Guanidines; Mass Spectrometry; Microbial Sensitivity Tests; Molecular Structure; Polymers

Abstract :

[en] In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently reported the identification of a series of linear guanidine derivatives and their antibacterial properties. A batch of a promising candidate for optimization studies (compound 1) turned out to be a mixture containing two unknown species with a better biological activity than the pure compound. This serendipitous discovery led us to investigate the chemical nature of the unknown components of the mixture. Through MS analysis coupled with design and synthesis we found that the components were spontaneously generated oligomers of the original compound. Preliminary biological evaluations eventually confirmed the broad-spectrum antibacterial activity of this new family of molecules. Interestingly the symmetric dimeric derivative (2) exhibited the best profile and it was selected as lead compound for further studies. © 2017 The Author(s).

Disciplines :

Microbiology
Life sciences: Multidisciplinary, general & others

Author, co-author :

Zamperini, C.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy, Lead Discovery Siena, Via Vittorio Alfieri 31, Castelnuovo, Berardenga, I-53019, Italy

MacCari, G.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

Deodato, D.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

Pasero, C.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

D'Agostino, I.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

Orofino, F.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

De Luca, F.; Department of Medical Biotechnology, University of Siena, Siena, I-53100, Italy

Dreassi, E.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy

Docquier, Jean-Denis ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines

Botta, M.; Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, I-53100, Italy, Lead Discovery Siena, Via Vittorio Alfieri 31, Castelnuovo, Berardenga, I-53019, Italy, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, United States

Language :

English

Title :

Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents

Publication date :

2017

Journal title :

Scientific Reports

eISSN :

2045-2322

Publisher :

Nature Publishing Group

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 November 2020

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