DNA binding and anticancer activity of naphthalimides with 4-hydroxyl-alkylamine side chains at different lengths

Bioorg Med Chem Lett. 2012 Jan 15;22(2):937-41. doi: 10.1016/j.bmcl.2011.12.018. Epub 2011 Dec 8.

Abstract

A series of novel naphthalimide derivatives modified with various hydroxyl-alkylamines at 4-position have been synthesized. Their DNA binding properties were investigated by UV-Vis, fluoescence, and circular dichroism (CD) spectroscopies and thermal denaturation. The results showed that compounds 3a-e as the DNA intercalator exhibited middle binding affinities with Ct-DNA. The anticancer activities of 3a-e were preliminarily evaluated, compounds 3c and 3e exhibited potent anticancer activities against Bel-7402 cell line with IC(50) values of 5.57 and 9.17μM, respectively. More interestingly, enhancement of the fluorescence emission was found in the complexes of 3a-e with Ct-DNA, especially for 3c. This would make these compounds as potential DNA staining agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites / drug effects
  • Cattle
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / chemistry
  • DNA / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans
  • Molecular Structure
  • Naphthalimides / chemical synthesis
  • Naphthalimides / chemistry
  • Naphthalimides / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Temperature

Substances

  • Amines
  • Antineoplastic Agents
  • Naphthalimides
  • DNA
  • calf thymus DNA