N1-Benzofused Modification of Fluoroquinolones Reduces Activity Against Gram-Negative Bacteria.

ABSTRACT: The fluoroquinolone class of antibiotics has a well-established structure-activity relationship (SAR) and a long history in the clinic, but the effect of electron-rich benzofused substituents at the N1 position remains poorly explored. Because groups at this position are part of the topoisomerase-DNA binding complex and form a hydrophobic interaction with the major groove of DNA, it was hypothesized that an electron-rich benzofused N1 substituent could enhance this interaction. Molecular modeling techniques were employed to evaluate the binding of certain N1-modified fluoroquinolones to DNA gyrase targets from both Staphylococcus aureus and Klebsiella pneumoniae species compared with ciprofloxacin and norfloxacin. Seven N1-modified fluoroquinolones were subsequently synthesiz

SUBMITTER: Laws M 

PROVIDER: S-EPMC7271024 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature