Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity

Elien Peeters, Geert Hooyberghs, Stijn Robijns, Kai Waldrant, Ami De Weerdt, Nicolas Delattin, Veerle Liebens, SonǍ Kucharíková, Helene Tournu, Natalie Verstraeten, Barbara Dovgan, Lenart Girandon, Mirjam Fröhlich, Katrijn De Brucker, Patrick Van Dijck, Jan Michiels, Bruno P.A. Cammue, Karin Thevissen, Jozef Vanderleyden, Erik Van Der EyckenHans P. Steenackers

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Wepreviously synthesized several series of compounds, based on the 5-Aryl-2-Aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1-and 2N-substituted 5-Aryl-2-Aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Grampositive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2Ndisubstituted 5-Aryl-2-Aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-Aryl-2-Aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-Aryl-2-Aminoimidazole scaffold allows fine-Tuning of both the antibiofilm activity spectrum and toxicity.

Original languageEnglish (US)
Pages (from-to)6483-6497
Number of pages15
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Biofilms
Gram-Positive Bacteria
Candida albicans
Gram-Negative Bacteria
Fungi
Bacteria
2-aminoimidazole
Bone and Bones
Cell Line
Salmonella enterica
Poisons
Eukaryotic Cells
Pseudomonas aeruginosa
Orthopedics
Cell Survival
Calcium

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity. / Peeters, Elien; Hooyberghs, Geert; Robijns, Stijn; Waldrant, Kai; De Weerdt, Ami; Delattin, Nicolas; Liebens, Veerle; Kucharíková, SonǍ; Tournu, Helene; Verstraeten, Natalie; Dovgan, Barbara; Girandon, Lenart; Fröhlich, Mirjam; De Brucker, Katrijn; Van Dijck, Patrick; Michiels, Jan; Cammue, Bruno P.A.; Thevissen, Karin; Vanderleyden, Jozef; Van Der Eycken, Erik; Steenackers, Hans P.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 11, 01.11.2016, p. 6483-6497.

Research output: Contribution to journalArticle

Peeters, E, Hooyberghs, G, Robijns, S, Waldrant, K, De Weerdt, A, Delattin, N, Liebens, V, Kucharíková, S, Tournu, H, Verstraeten, N, Dovgan, B, Girandon, L, Fröhlich, M, De Brucker, K, Van Dijck, P, Michiels, J, Cammue, BPA, Thevissen, K, Vanderleyden, J, Van Der Eycken, E & Steenackers, HP 2016, 'Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity', Antimicrobial Agents and Chemotherapy, vol. 60, no. 11, pp. 6483-6497. https://doi.org/10.1128/AAC.00035-16
Peeters, Elien ; Hooyberghs, Geert ; Robijns, Stijn ; Waldrant, Kai ; De Weerdt, Ami ; Delattin, Nicolas ; Liebens, Veerle ; Kucharíková, SonǍ ; Tournu, Helene ; Verstraeten, Natalie ; Dovgan, Barbara ; Girandon, Lenart ; Fröhlich, Mirjam ; De Brucker, Katrijn ; Van Dijck, Patrick ; Michiels, Jan ; Cammue, Bruno P.A. ; Thevissen, Karin ; Vanderleyden, Jozef ; Van Der Eycken, Erik ; Steenackers, Hans P. / Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 11. pp. 6483-6497.
@article{5667462b9682440c80c760a116d3588a,
title = "Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity",
abstract = "Wepreviously synthesized several series of compounds, based on the 5-Aryl-2-Aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1-and 2N-substituted 5-Aryl-2-Aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Grampositive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2Ndisubstituted 5-Aryl-2-Aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-Aryl-2-Aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-Aryl-2-Aminoimidazole scaffold allows fine-Tuning of both the antibiofilm activity spectrum and toxicity.",
author = "Elien Peeters and Geert Hooyberghs and Stijn Robijns and Kai Waldrant and {De Weerdt}, Ami and Nicolas Delattin and Veerle Liebens and SonǍ Kuchar{\'i}kov{\'a} and Helene Tournu and Natalie Verstraeten and Barbara Dovgan and Lenart Girandon and Mirjam Fr{\"o}hlich and {De Brucker}, Katrijn and {Van Dijck}, Patrick and Jan Michiels and Cammue, {Bruno P.A.} and Karin Thevissen and Jozef Vanderleyden and {Van Der Eycken}, Erik and Steenackers, {Hans P.}",
year = "2016",
month = "11",
day = "1",
doi = "10.1128/AAC.00035-16",
language = "English (US)",
volume = "60",
pages = "6483--6497",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Modulation of the substitution pattern of 5-Aryl-2-Aminoimidazoles allows fine-Tuning of their antibiofilm activity spectrum and toxicity

AU - Peeters, Elien

AU - Hooyberghs, Geert

AU - Robijns, Stijn

AU - Waldrant, Kai

AU - De Weerdt, Ami

AU - Delattin, Nicolas

AU - Liebens, Veerle

AU - Kucharíková, SonǍ

AU - Tournu, Helene

AU - Verstraeten, Natalie

AU - Dovgan, Barbara

AU - Girandon, Lenart

AU - Fröhlich, Mirjam

AU - De Brucker, Katrijn

AU - Van Dijck, Patrick

AU - Michiels, Jan

AU - Cammue, Bruno P.A.

AU - Thevissen, Karin

AU - Vanderleyden, Jozef

AU - Van Der Eycken, Erik

AU - Steenackers, Hans P.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Wepreviously synthesized several series of compounds, based on the 5-Aryl-2-Aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1-and 2N-substituted 5-Aryl-2-Aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Grampositive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2Ndisubstituted 5-Aryl-2-Aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-Aryl-2-Aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-Aryl-2-Aminoimidazole scaffold allows fine-Tuning of both the antibiofilm activity spectrum and toxicity.

AB - Wepreviously synthesized several series of compounds, based on the 5-Aryl-2-Aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1-and 2N-substituted 5-Aryl-2-Aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Grampositive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2Ndisubstituted 5-Aryl-2-Aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-Aryl-2-Aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-Aryl-2-Aminoimidazole scaffold allows fine-Tuning of both the antibiofilm activity spectrum and toxicity.

UR - http://www.scopus.com/inward/record.url?scp=84994894107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994894107&partnerID=8YFLogxK

U2 - 10.1128/AAC.00035-16

DO - 10.1128/AAC.00035-16

M3 - Article

C2 - 27550355

AN - SCOPUS:84994894107

VL - 60

SP - 6483

EP - 6497

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 11

ER -