Design and synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrids as anti-tumour agents

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1933-5. doi: 10.1016/s0960-894x(02)00326-8.

Abstract

The facile synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrid analogues is described. The compounds are prepared with varying degrees of linker length in order to probe the structural requirements for optimal in vitro anti-tumour activity. Some of these new hybrid compounds showed higher cytotoxic activity than the existing natural and synthetic pyrrolo[2,1-c][1,4]benzodiazepines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Benzodiazepines / chemical synthesis*
  • Benzodiazepines / metabolism
  • Benzodiazepines / pharmacology*
  • DNA / metabolism
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Lethal Dose 50
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / metabolism
  • Naphthalenes / pharmacology*
  • Pyrroles / chemical synthesis*
  • Pyrroles / metabolism
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Naphthalenes
  • Pyrroles
  • Benzodiazepines
  • DNA