title: Neomycin-phenolic conjugates: polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding.
abstract: Here we present a proof-of-concept study, combining two known antimicrobial agents into a hybrid structure in order to develop an emergent cationic detergent-like interaction with the bacterial membrane. Six amphiphilic conjugates were prepared by copper (I)-catalyzed 1,3-dipolar cycloaddition between a neomycin B-derived azide and three alkyne-modified phenolic disinfectants. Three conjugates displayed good activity against a variety of clinically relevant Gram positive and Gram negative bacteria, including MRSA, without the high level of hemolysis or strong binding to serum proteins commonly observed with other cationic antimicrobial peptides and detergents.
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: Findlay
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Frank
authors.initials: F
authors.lastname: Schweizer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D006461:Hemolysis / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D015394:Molecular Structure; D009355:Neomycin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology; D000071228:Polyelectrolytes; D011485:Protein Binding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009355:Neomycin; D010636:Phenols; D011073:Polyamines; D000071228:Polyelectrolytes; D012710:Serum Albumin, Bovine