Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones

Kevin R. Marks, Muhammad Malik, Arkady Mustaev, Hiroshi Hiasa, Karl Drlica, Robert J. Kerns

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Novel fluoroquinolone derivatives substituted with a 2-thioalkyl moiety, with and without a concomitant 3-carboxylate group, were synthesized to evaluate the effect of C-2 thioalkyl substituents on gyrase binding and inhibition. The presence of a 2-thioalkyl group universally decreased activity as compared to parent fluoroquinolones. However, with derivatives of moxifloxacin the presence of either a 2-thioalkyl group or a 3-carboxylate moiety increased activity over the 2,3-unsubstituted derivative. Energy minimization of structures provides an explanation for relative activities of fluoroquinolones having a C-2 thio moiety.

Original languageEnglish (US)
Pages (from-to)4585-4588
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number15
DOIs
StatePublished - Aug 1 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Keywords

  • Antibacterial
  • DNA gyrase
  • Fluoroquinolone
  • Moxifloxacin
  • Ulifloxacin

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