Human cancerous and healthy cell cytotoxicity studies of a chiral μ-dicarbene-digold(I) metallamacrocycle

Dalton Trans. 2013 May 28;42(20):7440-6. doi: 10.1039/c3dt32844a.

Abstract

A novel eighteen membered chiral macrocyclic dicarbene-digold complex [(μ-diNHC)Au(I)]2[OTF]2 (8-(+/-)) was synthesized and characterized. Starting with enantiopure diNHC imidazolium salt ligand precursors enables access to the enantiopure versions of the digold(I) metallamacrocycles, 8-(+) and 8-(-). In vitro cytotoxicity studies indicate 8-(+/-) is moderately cytotoxic to both healthy and cancerous cell-lines, with no specificity. Confocal microscopy indicates the digold metallamacrocycle penetrates the cell membrane and causes cell death via apoptosis, as evidenced by DNA electrophoresis. The complex 8-(+/-) is characterized by a combination of NMR techniques (gDQCOSY, gHSQC, gHMBC and ROESY), single crystal X-ray diffraction, and combustion analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Carbolines / chemical synthesis*
  • Carbolines / pharmacology
  • Carbolines / therapeutic use
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Cytotoxins / chemical synthesis*
  • Cytotoxins / pharmacology
  • Cytotoxins / therapeutic use
  • Gold / chemistry*
  • Gold / pharmacology
  • Gold / therapeutic use
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Neoplasms* / drug therapy
  • Stereoisomerism
  • X-Ray Diffraction

Substances

  • Carbolines
  • Cytotoxins
  • Gold
  • dicarbine