title: Novel inhibitors of bacterial two-component systems with gram positive antibacterial activity: pharmacophore identification based on the screening hit closantel.
abstract: This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. Closantel (1) was found to inhibit a two-component system and to have antibacterial activity against drug resistant S. aureus and E. faecium.
authors.affiliation: R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hlasta
authors.forename: J P
authors.initials: JP
authors.lastname: Demers
authors.forename: B D
authors.initials: BD
authors.lastname: Foleno
authors.forename: S A
authors.initials: SA
authors.lastname: Fraga-Spano
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.forename: J J
authors.initials: JJ
authors.lastname: Hilliard
authors.forename: M J
authors.initials: MJ
authors.lastname: Macielag
authors.forename: K A
authors.initials: KA
authors.lastname: Ohemeng
authors.forename: C M
authors.initials: CM
authors.lastname: Sheppard
authors.forename: Z
authors.initials: Z
authors.lastname: Sui
authors.forename: G C
authors.initials: GC
authors.lastname: Webb
authors.forename: M A
authors.initials: MA
authors.lastname: Weidner-Wells
authors.forename: H
authors.initials: H
authors.lastname: Werblood
authors.forename: J F
authors.initials: JF
authors.lastname: Barrett
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010766:Phosphorylation; D012458:Salicylanilides / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D012458:Salicylanilides; C023342:closantel