Open AccessIdentification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents
Author(s) -
Claudio Zamperini,
Giorgio Maccari,
Davide Deodato,
Carolina Pasero,
Ilaria D’Agostino,
Francesco Orofino,
Filomena De Luca,
Elena Dreassi,
Jean Denis Docquier,
Maurizio Botta
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08749-6
Subject(s) - guanidine , identification (biology) , alkyl , combinatorial chemistry , antibacterial activity , chemistry , biological activity , computational biology , pharmacology , biochemistry , biology , bacteria , organic chemistry , in vitro , genetics , botany
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.