Design, Synthesis, and Biological Evaluation of Hexacyclic Tetracyclines as Potent, Broad Spectrum Antibacterial Agents

J Med Chem. 2015 Jun 11;58(11):4703-12. doi: 10.1021/acs.jmedchem.5b00262. Epub 2015 May 20.

Abstract

A series of novel hexacyclic tetracycline analogues ("hexacyclines") was designed, synthesized, and evaluated for antibacterial activity against a wide range of clinically important bacteria isolates, including multidrug-resistant, Gram-negative pathogens. Valuable structure-activity relationships were identified, and several hexacyclines displayed potent, broad spectrum antibacterial activity, including promising anti-Pseudomonas aeruginosa activity in vitro and in vivo.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Drug Design*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Structure-Activity Relationship
  • Tetracyclines / pharmacology*
  • Thigh / microbiology

Substances

  • Anti-Bacterial Agents
  • Tetracyclines