Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors

Nizalapur, S; Ho, KKK; Kimyon, Ö; Yee, E; Berry, T; Manefield, M; Cranfield, CG; Willcox, M; Black, DSC; Kumar, N

Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors

Nizalapur, S Ho, KKK Kimyon, Ö Yee, E Berry, T

Manefield, M Cranfield, CG

Willcox, M Black, DSC Kumar, N

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Publication Type:: Journal Article
Citation:: Organic and Biomolecular Chemistry, 2016, 14 (14), pp. 3623 - 3637
Issue Date:: 2016-04-14

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Field	Value	Language
dc.contributor.author	Nizalapur, S	en_US
dc.contributor.author	Ho, KKK	en_US
dc.contributor.author	Kimyon, Ö	en_US
dc.contributor.author	Yee, E	en_US
dc.contributor.author	Berry, T https://orcid.org/0000-0002-2882-0313	en_US
dc.contributor.author	Manefield, M	en_US
dc.contributor.author	Cranfield, CG https://orcid.org/0000-0003-3608-5440	en_US
dc.contributor.author	Willcox, M	en_US
dc.contributor.author	Black, DSC	en_US
dc.contributor.author	Kumar, N	en_US
dc.date.issued	2016-04-14	en_US
dc.identifier.citation	Organic and Biomolecular Chemistry, 2016, 14 (14), pp. 3623 - 3637	en_US
dc.identifier.issn	1477-0520	en_US
dc.identifier.uri	http://hdl.handle.net/10453/43402
dc.description.abstract	© The Royal Society of Chemistry 2016. Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivatives via ring-opening reactions of N-hexanoyl, N-benzoyl and N-naphthoylisatins with N,N-dimethylethane-1,2-diamine and N,N-dimethylpropane-1,3-diamine. These were converted to both the hydrochloric acid (HCl) or quaternary ammonium iodide (MeI) salts and their antibacterial activity against Staphylococcus aureus was investigated by their zone-of-inhibition and minimum inhibitory concentration (MIC). The HCl salt 22b exhibited the lowest MIC of 16 μg mL-1, whereas the corresponding MeI salt 22c had a MIC of 39 μg mL-1. We also investigated the in vitro toxicity of active compounds against the MRC-5 normal human lung fibroblasts and their activity against established biofilm in S. aureus.	en_US
dc.relation	http://purl.org/au-research/grants/arc/DP160101664
dc.relation.ispartof	Organic and Biomolecular Chemistry	en_US
dc.relation.isbasedon	10.1039/c6ob00298f	en_US
dc.subject.classification	Organic Chemistry	en_US
dc.subject.mesh	Biofilms	en_US
dc.subject.mesh	Sulfonylurea Compounds	en_US
dc.subject.mesh	Peptides	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Microbial Sensitivity Tests	en_US
dc.subject.mesh	Molecular Mimicry	en_US
dc.title	Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors	en_US
dc.type	Journal Article
utslib.citation.volume	14	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0305 Organic Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.issue	14	en_US
pubs.publication-status	Published	en_US
pubs.volume	14	en_US

Abstract:

© The Royal Society of Chemistry 2016. Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivatives via ring-opening reactions of N-hexanoyl, N-benzoyl and N-naphthoylisatins with N,N-dimethylethane-1,2-diamine and N,N-dimethylpropane-1,3-diamine. These were converted to both the hydrochloric acid (HCl) or quaternary ammonium iodide (MeI) salts and their antibacterial activity against Staphylococcus aureus was investigated by their zone-of-inhibition and minimum inhibitory concentration (MIC). The HCl salt 22b exhibited the lowest MIC of 16 μg mL-1, whereas the corresponding MeI salt 22c had a MIC of 39 μg mL-1. We also investigated the in vitro toxicity of active compounds against the MRC-5 normal human lung fibroblasts and their activity against established biofilm in S. aureus.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/43402