2. Academic Validation
  3. Novel bacterial topoisomerase inhibitors derived from isomannide

Novel bacterial topoisomerase inhibitors derived from isomannide

  • Eur J Med Chem. 2020 Aug 1;199:112324. doi: 10.1016/j.ejmech.2020.112324.
Antony Okumu 1,  Yanran Lu 1,  Sheri Dellos-Nolan 2,  Jonathan L Papa 3,  Bryan Koci 4,  Nicholas T Cockroft 1,  Judith Gallucci 5,  Daniel J Wozniak 6,  Jack C Yalowich 3,  Mark J Mitton-Fry 7
Affiliations

Affiliations

  • 1 Division of Medicinal Chemistry and Pharmacognosy. The Ohio State University, Columbus, OH, 43210, USA.
  • 2 Microbial Infection and Immunity. The Ohio State University, Columbus, OH, 43210, USA.
  • 3 Division of Pharmaceutics and Pharmacology. The Ohio State University, Columbus, OH, 43210, USA.
  • 4 Eurofins Panlabs. St. Charles, MO, 63304, USA.
  • 5 Department of Chemistry and Biochemistry. The Ohio State University, Columbus, OH, 43210, USA.
  • 6 Microbial Infection and Immunity. The Ohio State University, Columbus, OH, 43210, USA; Department of Microbiology. The Ohio State University, Columbus, OH, 43210, USA.
  • 7 Division of Medicinal Chemistry and Pharmacognosy. The Ohio State University, Columbus, OH, 43210, USA. Electronic address: mitton-fry.1@osu.edu.
PMID: 32402932 DOI: 10.1016/j.ejmech.2020.112324
Abstract

A series of Novel Bacterial Topoisomerase Inhibitors (NBTIs) employing a linker derived from isomannide were synthesized and evaluated. Reduced hERG inhibition was observed compared to structure-matched analogues with different linkers, and compound 6 showed minimal proarrhythmic potential using an in vitro panel of cardiac ion channels. Compound 6 also displayed excellent activity against fluoroquinolone-resistant MRSA (MIC90 = 2 μg/mL) and other Gram-positive pathogens.

Keywords

Cystic fibrosis; DNA gyrase; MRSA; NBTI.

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