Hypoxia activated prodrugs of a 9-aza-anthrapyrazole derivative that has promising anticancer activity

J Med Chem. 2011 Dec 8;54(23):8224-7. doi: 10.1021/jm200984x. Epub 2011 Nov 4.

Abstract

Mono- and bis-N-oxides of a 9-aza-anthrapyrazole derivative having two 2-(dimethylamino)ethyl appendages were prepared by using a mild oxaziridine reagent. Biochemical and cell culture assays indicate that the bis-oxide is an inactive prodrug that readily converts to the active parent molecule under hypoxic conditions that are analogous to those present within certain tumors.

MeSH terms

  • Anthraquinones / chemical synthesis*
  • Anthraquinones / chemistry
  • Anthraquinones / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Cell Hypoxia
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Free Radicals / metabolism
  • Humans
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • Aza Compounds
  • Free Radicals
  • Prodrugs
  • Pyrazoles