Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as potential hypoxic cytotoxins and DNA-binders

Arch Pharm (Weinheim). 2000 Nov;333(11):387-93. doi: 10.1002/1521-4184(200011)333:11<387::aid-ardp387>3.0.co;2-n.

Abstract

Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Animals
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology*
  • Cell Line
  • Cell Survival / drug effects*
  • Clone Cells
  • Cytotoxins / chemical synthesis*
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology
  • DNA / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Oxides / chemical synthesis*
  • Oxides / chemistry
  • Oxides / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cytotoxins
  • Oxadiazoles
  • Oxides
  • DNA