title: Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors.
abstract: 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.
authors.affiliation: School of Chemistry, UNSW Australia, Sydney, NSW 2052, Australia. n.kumar@unsw.edu.au.
authors.forename: Shashidhar
authors.initials: S
authors.lastname: Nizalapur
authors.forename: Kitty K K
authors.initials: KK
authors.lastname: Ho
authors.forename: Önder
authors.initials: Ö
authors.lastname: Kimyon
authors.forename: Eugene
authors.initials: E
authors.lastname: Yee
authors.forename: Thomas
authors.initials: T
authors.lastname: Berry
authors.forename: Mike
authors.initials: M
authors.lastname: Manefield
authors.forename: Charles G
authors.initials: CG
authors.lastname: Cranfield
authors.forename: Mark
authors.initials: M
authors.lastname: Willcox
authors.forename: David StC
authors.initials: DS
authors.lastname: Black
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D018716:Molecular Mimicry; D010455:Peptides / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D013453:Sulfonylurea Compounds; C032160:glyoxamide