Oxoisoaporphine alkaloid derivatives: synthesis, DNA binding affinity and cytotoxicity

Eur J Med Chem. 2008 May;43(5):973-80. doi: 10.1016/j.ejmech.2007.07.004. Epub 2007 Jul 15.

Abstract

A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1-azabenzanthrone (general formula Ar-NHCO(CH(2))(n)NR(2), Ar=1-azabenzanthrone, n=1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure-activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n=2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aporphines / chemical synthesis*
  • Aporphines / chemistry
  • Aporphines / pharmacology*
  • Cell Line, Tumor
  • DNA / chemistry*
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Aporphines
  • DNA