title: Natural product derivatives with bactericidal activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis.
abstract: We have shown that the intentional engineering of a natural product biosynthesis pathway is a useful way to generate stereochemically complex scaffolds for use in the generation of combinatorial libraries that capture the structural features of both natural products and synthetic compounds. Analysis of a prototype library based upon nonactic acid lead to the discovery of triazole-containing nonactic acid analogs, a new structural class of antibiotic that exhibits bactericidal activity against drug resistant, Gram-positive pathogens including Staphylococcus aureus and Enterococcus faecalis.
authors.affiliation: Department of Chemistry, University of Montana, Missoula, MT 59812, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Phillips
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Smith
authors.forename: Brian R
authors.initials: BR
authors.lastname: Kusche
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Bessette
authors.forename: P Whitney
authors.initials: PW
authors.lastname: Swain
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bergmeier
authors.forename: Mark C
authors.initials: MC
authors.lastname: McMills
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Wright
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Priestley
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D018942:Macrolides; D014230:Triazoles; D014640:Vancomycin; C050476:nonactin
references.citation: Int J Antimicrob Agents. 2004 Mar;23 Suppl 1:S24-9
references.pmid: 15037325
references.citation: Curr Opin Microbiol. 2007 Jun;10(3):238-45
references.pmid: 17553731
references.citation: Chem Rev. 2006 Aug;106(8):3468-96
references.pmid: 16895337
references.citation: Biotechnol Prog. 2006 Sep-Oct;22(5):1354-7
references.pmid: 17022674
references.citation: J Am Chem Soc. 2005 Jun 8;127(22):7976-7
references.pmid: 15926797
references.citation: Bioorg Med Chem Lett. 2008 Jul 15;18(14):3946-9
references.pmid: 18585037
references.citation: Org Lett. 2006 Feb 2;8(3):443-5
references.pmid: 16435855
references.citation: Nat Prod Rep. 2000 Jun;17(3):215-34
references.pmid: 10888010
references.citation: Bioorg Med Chem Lett. 2009 Feb 15;19(4):1233-5
references.pmid: 19167217
references.citation: FEMS Microbiol Rev. 2006 Jul;30(4):530-63
references.pmid: 16774586