Aza-analogues of the marine pyrroloquinoline alkaloids wakayin and tsitsikammamines: synthesis and topoisomerase inhibition

Bioorg Med Chem Lett. 2006 Jan 15;16(2):427-9. doi: 10.1016/j.bmcl.2005.09.063. Epub 2005 Oct 18.

Abstract

Two aza-analogues of the marine pyrroloquinoline alkaloids wakayin and tsitsikammamines A and B have been synthesized. The strategy used was based on a 1,3-dipolar cycloaddition reaction between indole 4,7-dione and a diazo-aminopropane derivative. One of the two analogues partially inhibits human topoisomerase I, whereas synthetic intermediates inhibit the enzyme DNA cleavage activity at a concentration comparable to that of the control drug camptothecin.

MeSH terms

  • Animals
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Cyclization
  • Humans
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology
  • Molecular Structure
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry*
  • Quinolines / pharmacology
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*

Substances

  • Aza Compounds
  • Indole Alkaloids
  • Pyrroles
  • Quinolines
  • Topoisomerase I Inhibitors
  • pyrroloquinoline
  • tsitsikammamine A
  • tsitsikammamine B
  • wakayin