title: Synthesis of linear and cyclic guazatine derivatives endowed with antibacterial activity.
abstract: Antibiotic resistance has reached alarming levels in many clinically-relevant human pathogens, and there is an increasing clinical need for new antibiotics active on drug-resistant Gram-negative pathogens who rapidly evolve towards pandrug resistance phenotypes. Here, we report on two related classes of guanidinic compounds endowed with antibacterial activity. The two best compounds (9a and 13d) exhibited the most potent antibacterial activity with MIC values ranging 0.12-8 μg/ml with most tested pathogens, including both Gram-positive and Gram-negative bacteria. Interestingly, MIC values were not affected (1-8 μg/ml) when measured using recent clinical isolates with various antibiotic resistance determinants. The results reported herein identify guazatine derivatives as an interesting starting point for the optimization of a potentially novel class of antibacterial agents.
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Maccari
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sanfilippo
authors.affiliation: Department of Medical Biotechnology, University of Siena, I-53100 Siena, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: De Luca
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Deodato
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Casian
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Dasso Lang
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Dreassi
authors.affiliation: Department of Medical Biotechnology, University of Siena, I-53100 Siena, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Rossolini
authors.affiliation: Department of Medical Biotechnology, University of Siena, I-53100 Siena, Italy.
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Docquier
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, I-53100 Siena, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA; Lead Discovery Siena s.r.l, Via Vittorio Alfieri 31, I-53019 Castelnuovo Berardenga, Italy. Electronic address: botta.maurizio@gmail.com.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006146:Guanidines / Q000737:chemistry*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D006146:Guanidines; C012343:guazatine
keywords: Antibacterial; Drug resistant bacteria; Guanidinic compounds; Macrocycles