title: A Phytochemical-Halogenated Quinoline Combination Therapy Strategy for the Treatment of Pathogenic Bacteria.
abstract: With the continued rise of drug-resistant bacterial infections coupled with the current discouraging state of the antibiotic pipeline, the need for new antibacterial agents that operate through unique mechanisms compared with conventional antibiotics and work in synergy with other agents is at an all-time high. We have discovered that gallic acid, a plant-derived phytochemical, dramatically potentiates the antibacterial activities of several halogenated quinolines (up to 11,800-fold potentiation against Staphylococcus aureus) against pathogenic bacteria, including drug-resistant clinical isolates. S. aureus demonstrated the highest sensitivity towards gallic acid-halogenated quinoline combinations, including one halogenated quinoline that demonstrated potentiation of biofilm eradication activity against a methicillin-resistant S. aureus (MRSA) clinical isolate. During our studies, we also demonstrated that these halogenated quionlines operate through an interesting metal(II) cation-dependent mechanism and display promising mammalian cytotoxicity.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610 (USA).
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Abouelhassan
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610 (USA).
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Garrison
authors.affiliation: Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610 (USA).|College of Pharmacy, Nankai University, 94 Weijin Rd, Tianjin 300071 (P. R. China).
authors.forename: Fang
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610 (USA).
authors.forename: Verrill M
authors.initials: VM
authors.lastname: Norwood
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610 (USA).
authors.forename: Minh Thu
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610 (USA).
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610 (USA). rhuigens@cop.ufl.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Huigens
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005707:Gallic Acid / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D064209:Phytochemicals; D011804:Quinolines; D005707:Gallic Acid
keywords: antibacterial potentiation; biofilm eradication; combination antibacterial therapy; drug discovery; halogenated quinolones; phytochemicals