title: Allicin-inspired thiolated fluoroquinolones as antibacterials against ESKAPE pathogens.
abstract: Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis.
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States.
authors.forename: Jordan G
authors.initials: JG
authors.lastname: Sheppard
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States; Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States. Electronic address: longt@marshall.edu.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D004220:Disulfides; D024841:Fluoroquinolones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D013441:Sulfinic Acids / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004220:Disulfides; D024841:Fluoroquinolones; D013438:Sulfhydryl Compounds; D013441:Sulfinic Acids; C006452:allicin
keywords: Allicin; Antibiotic; Fluoroquinolone; Glutathione; MRSA