Novel pyridyl nitrofuranyl isoxazolines show antibacterial activity against multiple drug resistant Staphylococcus species

Bioorg Med Chem. 2017 Aug 1;25(15):3971-3979. doi: 10.1016/j.bmc.2017.05.037. Epub 2017 May 19.

Abstract

A novel series of pyridyl nitrofuranyl isoxazolines were synthesized and evaluated for their antibacterial activity against multiple drug resistant (MDR) Staphylococcus strains. Compounds with piperazine linker between the pyridyl group and isoxazoline ring showed better activity when compared to compounds without the piperazine linker. 3-Pyridyl nitrofuranyl isoxazoline with a piperazine linker was found to be more active than corresponding 2-and 4-pyridyl analogues with MICs in the range of 4-32µg/mL against MDR Staphylococcus strains. The eukaryotic toxicity of the compounds was tested by MTT assay and were found to be non-toxic against both non-tumour lung fibroblast WI-38 and cervical cancer cell line HeLa. The most active pyridyl nitrofuranyl isoxazoline compound showed improved activity against a panel of Staphylococcus strains compared to nitrofuran group containing antibiotic nitrofurantoin.

Keywords: Antibacterial activity; Antimicrobial resistance; MRSA; Medicinal chemistry; Nitrofuran isoxazoline; Structure activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Nitrofurantoin / chemistry*
  • Oxazoles / chemistry
  • Oxazoles / pharmacology*
  • Spectrum Analysis
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Oxazoles
  • Nitrofurantoin