title: Non-transpeptidase binding arylthioether β-lactams active against Mycobacterium tuberculosis and Moraxella catarrhalis.
abstract: The prevalence of drug resistance in both clinical and community settings as a consequence of alterations of biosynthetic pathways, enzymes or cell wall architecture is a persistent threat to human health. We have designed, synthesized, and tested a novel class of non-transpeptidase, β-lactamase resistant monocyclic β-lactams that carry an arylthio group at C4. These thioethers exhibit inhibitory and cidal activity against serine β-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n=8) β-lactamase producing Moraxella catarrhalis clinical isolates.
authors.affiliation: Department of Chemistry, American University, Washington, DC 20016, USA.
authors.forename: Tim N
authors.initials: TN
authors.lastname: Beck
authors.affiliation: Department of Chemistry, American University, Washington, DC 20016, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Lloyd
authors.affiliation: Department of Chemistry, American University, Washington, DC 20016, USA.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Kuskovsky
authors.affiliation: Department of Chemistry, American University, Washington, DC 20016, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Minah
authors.affiliation: Tuberculosis Research Section, LCID, NIAID, NIH 33 North Drive, Bldg 33, Rm 2W20C, Bethesda, MD 20892, USA.
authors.forename: Kriti
authors.initials: K
authors.lastname: Arora
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Chicago, IL 60515, USA.
authors.forename: Balbina J
authors.initials: BJ
authors.lastname: Plotkin
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Chicago, IL 60515, USA.
authors.forename: Jacalyn M
authors.initials: JM
authors.lastname: Green
authors.affiliation: Tuberculosis Research Section, LCID, NIAID, NIH 33 North Drive, Bldg 33, Rm 2W20C, Bethesda, MD 20892, USA.
authors.forename: Helena I
authors.initials: HI
authors.lastname: Boshoff
authors.affiliation: Tuberculosis Research Section, LCID, NIAID, NIH 33 North Drive, Bldg 33, Rm 2W20C, Bethesda, MD 20892, USA.
authors.forename: Clifton
authors.initials: C
authors.lastname: Barry
authors.affiliation: Naval Research Laboratory, Code 6930 4555 Overlook Ave., Washington, DC 20375, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Deschamps
authors.affiliation: Department of Chemistry, American University, Washington, DC 20016, USA. Electronic address: mkonak@american.edu.
authors.forename: Monika I
authors.initials: MI
authors.lastname: Konaklieva
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000201:enzymology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams
keywords: Antimicrobial resistance; Moraxella catarrhalis; Mycobacterium tuberculosis; β-Lactams