Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo[2,1-c][1,4]benzodiazepines related to anthramycin

J Med Chem. 2001 Oct 25;44(22):3754-7. doi: 10.1021/jm010937q.

Abstract

A new 7,8-methylenedioxy analogue (4) of (+)-porothramycin B (2) and its water-soluble sodium bisulfite derivative (15) have been synthesized in high yields and have been shown to exhibit high cytotoxic activities against several tumor cell lines. The new pyrrolo[2,1-c][1,4]benzodiazepine 4 was as effective against the resistant cell lines as against the doxorubicin-sensitive cell lines tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthramycin / analogs & derivatives
  • Anthramycin / chemical synthesis*
  • Anthramycin / chemistry
  • Anthramycin / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Humans
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • (11R,11aS)-2-(N,N-dimethyl)acrylamide-1,10,11,11a-tetrahydro-11-methoxy-7,8-methylenedioxy-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one
  • Antineoplastic Agents
  • Anthramycin
  • Doxorubicin