Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol side chains

Bioorg Med Chem Lett. 2012 Oct 15;22(20):6347-51. doi: 10.1016/j.bmcl.2012.08.079. Epub 2012 Aug 30.

Abstract

A series of phenanthrene imidazole with polyglycol side chain (2a-2c and 3a-3c) were synthesized and characterized by IR, NMR and MS. The cytotoxicity of 2a-2c and 3a-3c against cancer cell lines (HL-60, BGC-823, Bel-7402 and KB) in vitro were measured using MTT method. The DNA binding properties of 3a-3c were investigated by UV, fluorescence, CD spectroscopies and thermal denaturation. The results indicate that 2a exhibits higher cytotoxicity than cisplatin against BGC-823 and Bel-7402 cell lines, 3b and 3c exhibit higher cytotoxicity than 2b and 2c against BGC-823, Bel-7402 and KB cell lines. The cytotoxic effect of 2a-2c decrease with the increase of side chains length, the cytotoxic effect of 3a-3c increased with the increasing length of side chains against BGC-823, Bel-7402 and KB cell lines. Compounds 3a-3c intercalated DNA with a vertical orientation in the intercalation pocket. The binding constants of 3a-3c with Ct-DNA are 1.68×10(6), 1.51×10(6) and 0.709×10(6)M(-1), respectively. The binding affinity of 3a-3c with Ct-DNA trended to decrease with the increasing length of polyglycol side chains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • DNA / metabolism*
  • Glycols / chemistry
  • Glycols / pharmacology
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology
  • Neoplasms / drug therapy
  • Phenanthrenes / chemistry*
  • Phenanthrenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Glycols
  • Imidazoles
  • Intercalating Agents
  • Phenanthrenes
  • phenanthrene
  • imidazole
  • DNA