Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents
Claudio Zamperini,Giorgio Maccari,Davide Deodato,Carolina Pasero,Ilaria D'Agostino,Francesco Orofino,F. De Luca,Elena Dreassi,Jean Denis Docquier,Maurizio Botta,Maurizio Botta +10 more
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TLDR
A batch of a promising candidate for optimization studies turned out to be a mixture containing two unknown species with a better biological activity than the pure compound, and this serendipitous discovery led to investigate the chemical nature of the unknown components of the mixture.Abstract:
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.read more
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Rational Design of Dimeric Lysine N-Alkylamides as Potent and Broad-Spectrum Antibacterial Agents
Youhong Niu,Minghui Wang,Cao Yafei,Alekhya Nimmagadda,Jianxing Hu,Yan-Fen Wu,Jianfeng Cai,Xin-Shan Ye +7 more
TL;DR: It is suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.
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Antimicrobial drugs bearing guanidine moieties: A review.
TL;DR: An overview of recent advances in hit-to-lead development studies of antimicrobial guanidine-containing compounds with the aim to highlight their structural diversity and the pharmacological relevance of the moiety to drug activity is provided in this article.
Journal ArticleDOI
Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization.
Carolina Pasero,Ilaria D'Agostino,Filomena De Luca,Claudio Zamperini,Davide Deodato,Giuseppina I. Truglio,Filomena Sannio,Rosita Del Prete,Teresa Ferraro,Daniela Visaggio,Arianna Mancini,Mario B. Guglielmi,Paolo Visca,Jean Denis Docquier,Maurizio Botta,Maurizio Botta +15 more
TL;DR: An alkyl-guanidine derivative, characterized by a symmetrical dimeric structure, is reported as a good candidate for further developments, with a high antibacterial activity against both Gram-positive and Gram-negative strains.
Journal ArticleDOI
The chemistry and biology of guanidine secondary metabolites.
Roberto G. S. Berlinck,Darlon I. Bernardi,Taicia Pacheco Fill,Alessandra A. G. Fernandes,Igor D. Jurberg +4 more
TL;DR: The topics include the discovery of new metabolites, total synthesis of natural guanidine compounds, biological activity and mechanism-of-action, biosynthesis and ecological functions.
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Ammonium and guanidine carbosilane dendrimers and dendrons as microbicides
Irene Heredero-Bermejo,José Manuel Hernández-Ros,Leticia Sánchez-García,Marek Maly,Cristina Verdú-Expósito,Juan Soliveri,F. Javier de la Mata,José Luis Copa-Patiño,Jorge Pérez-Serrano,Javier Sánchez-Nieves,Rafael Gómez +10 more
TL;DR: Molecular dynamics study of interactions between selected dendrimers and anionic phospholipid bilayers indicates possible connections between the antibacterial activity and interaction modes.
References
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Journal ArticleDOI
Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America
Helen W. Boucher,George H. Talbot,John S. Bradley,John S. Bradley,John E. Edwards,John E. Edwards,David N. Gilbert,Louis B. Rice,Louis B. Rice,Michael Scheld,Brad Spellberg,Brad Spellberg,John G. Bartlett +12 more
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Journal Article
The Antibiotic Resistance Crisis: Part 1: Causes and Threats
TL;DR: Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development.
Tackling drug-resistant infections globally: final report and recommendations
TL;DR: Suggested reading taken from the last 12 months of the Commission’s weekly publication “On the Radar” highlights papers and reporting exploring the evidence for the effectiveness of antimicrobial stewardship in hospitals, the scope of the problem of antimacterial resistance, and some specific stewardship strategies.