Organogermanium compound, Ge-132, forms complexes with adrenaline, ATP and other physiological cis-diol compounds

Future Med Chem. 2015;7(10):1233-46. doi: 10.4155/fmc.15.62.

Abstract

Background: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds.

Results: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP.

Conclusion: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Catecholamines / metabolism
  • Cell Line
  • Crystallography, X-Ray
  • Epinephrine / metabolism*
  • Germanium / chemistry
  • Germanium / pharmacology
  • Humans
  • Hydrolysis
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Propionates

Substances

  • 3-(trihydroxygermyl)propanoic acid
  • Catecholamines
  • Organometallic Compounds
  • Propionates
  • Germanium
  • propagermanium
  • Adenosine Triphosphate
  • Epinephrine