title: Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy.
abstract: Staphylococcus aureus and Staphylococcus epidermidis are recognized as the most frequent cause of biofilm-associated nosocomial and indwelling medical device infections. Biofilm-associated infections are known to be highly resistant to our current arsenal of clinically used antibiotics and antibacterial agents. To exacerbate this problem, no therapeutic option exists that targets biofilm-dependent machinery critical to Staphylococcal biofilm formation and maintenance. Here, we describe the discovery of a series of quinoline small molecules that demonstrate potent biofilm dispersal activity against methicillin-resistant S. aureus and S. epidermidis using a scaffold hopping strategy. This interesting class of quinolines also has select synthetic analogues that demonstrate potent antibacterial activity and biofilm inhibition against S. aureus and S. epidermidis.
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA.
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Abouelhassan
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Garrison
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA.
authors.forename: Gena M
authors.initials: GM
authors.lastname: Burch
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: Wong
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA.
authors.forename: Verrill M
authors.initials: VM
authors.lastname: Norwood
authors.affiliation: University of Florida, Department of Medicinal Chemistry, College of Pharmacy, 1600 SW Archer Rd., Gainesville, FL 32610, USA. Electronic address: rhuigens@cop.ufl.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Huigens
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; C037219:quinoline
keywords: Antibacterial agent; Biofilm dispersal agent; Biofilm inhibitor; Drug discovery; Quinoline