Article (Scientific journals)
Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization
Pasero, C.; D'Agostino, I.; De Luca, F. et al.
2018In Journal of Medicinal Chemistry, 61 (20), p. 9162-9176
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Keywords :
Caco-2 cell line; Alkylation; Anti-Bacterial Agents; Caco-2 Cells; Guanidine; Humans; Microbial Sensitivity Tests; Permeability; Structure-Activity Relationship
Abstract :
[en] Nowadays, the increasing of multidrug-resistant pathogenic bacteria represents a serious threat to public health, and the lack of new antibiotics is becoming a global emergency. Therefore, research in antibacterial fields is urgently needed to expand the currently available arsenal of drugs. We have recently reported an alkyl-guanidine derivative (2), characterized by a symmetrical dimeric structure, as a good candidate for further developments, with a high antibacterial activity against both Gram-positive and Gram-negative strains. In this study, starting from its chemical scaffold, we synthesized a small library of analogues. Moreover, biological and in vitro pharmacokinetic characterizations were conducted on some selected derivatives, revealing notable properties: broad-spectrum profile, activity against resistant clinical isolates, and appreciable aqueous solubility. Interestingly, 2 seems neither to select for resistant strains nor to macroscopically alter the membranes, but further studies are required to determine the mode of action. Copyright © 2018 American Chemical Society.
Disciplines :
Life sciences: Multidisciplinary, general & others
Microbiology
Author, co-author :
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
De Luca, F.;  Department of Medical Biotechnology, University of Siena, Siena, I-53100, Italy
Zamperini, C.;  Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Siena, I-53100, Italy, Lead Discovery Siena S.r.l., Via Vittorio Alfieri 31, Castelnuovo Berardenga, I-53019, Italy
Deodato, D.;  Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Siena, I-53100, Italy
Truglio, G. I.;  Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Siena, I-53100, Italy
Sannio, F.;  Department of Medical Biotechnology, University of Siena, Siena, I-53100, Italy
Del Prete, R.;  Department of Medical Biotechnology, University of Siena, Siena, I-53100, Italy
Ferraro, T.;  Lead Discovery Siena S.r.l., Via Vittorio Alfieri 31, Castelnuovo Berardenga, I-53019, Italy
Visaggio, D.;  Department of Sciences, Roma Tre University, Rome, 00146, Italy
Mancini, A.;  Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Siena, I-53100, Italy
Guglielmi, M. B.;  Biogem, Research Institute, Ariano Irpino, AV, Italy
Visca, P.;  Department of Sciences, Roma Tre University, Rome, 00146, 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 S.r.l., Via Vittorio Alfieri 31, Castelnuovo Berardenga, I-53019, Italy, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, BioLife Science Building, 1900 North 12th Street, Philadelphia, PA 19122, United States
More authors (5 more) Less
Language :
English
Title :
Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization
Publication date :
2018
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
American Chemical Society
Volume :
61
Issue :
20
Pages :
9162-9176
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 November 2020

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