Synthesis, antitumor activity, molecular modeling, and DNA binding properties of a new series of imidazonaphthalimides

J Med Chem. 2002 Dec 19;45(26):5813-6. doi: 10.1021/jm020950q.

Abstract

A series of mono and bisintercalators based on the 5,8-dihydrobenz[de]imidazo[4,5-g]isoquinoline-4,6-dione system were synthesized and evaluated for growth inhibitory properties in several human cell lines. All target compounds showed activity in the micromolar range. Representative compounds were evaluated using UV--vis spectroscopy and viscosimetric determinations, showing that they behave as DNA intercalators. Molecular modeling techniques were used in order to rationalize the moderate activity observed for bisnaphthalimides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Intercalating Agents / chemical synthesis*
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology
  • Models, Molecular
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • Intercalating Agents
  • Naphthalenes