Glycerylphytate compounds with tunable ion affinity and osteogenic properties

Sci Rep. 2019 Aug 7;9(1):11491. doi: 10.1038/s41598-019-48015-5.

Abstract

Phytic acid (PA) is a natural-occurring antioxidant, which plays an important role in many biological processes. PA is recognized as a potent inhibitor of lipid peroxidation because of its high affinity to multivalent cations, and it can play a role in osteogenic processes. However, its powerful chelating capacity is controversial because it can lead to a severe reduction of mineral availability in the organism. For this reason, compounds with beneficial biological properties of PA, but a modular ion binding capacity, are of high interest. In this work, we report the synthesis and physicochemical characterization of two hydroxylic derivatives of PA, named glycerylphytates (GPhy), through a condensation reaction of PA with glycerol (G). Both derivatives present antioxidant properties, measured by ferrozine/FeCl2 method and chelating activity with calcium ions depending on the content of glyceryl groups incorporated. Besides, the hydroxylic modification not only modulates the ion binding affinity of derivatives but also improves their cytocompatibility in human bone marrow mesenchymal cells (MSCs). Furthermore, GPhy derivatives display osteogenic properties, confirmed by COL1A and ALPL expression depending on composition. These positive features convert GPhy compounds into potent alternatives for those skeletal diseases treatments where PA is tentatively applied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Calcium / metabolism
  • Cations, Divalent / metabolism
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology*
  • Collagen Type I / metabolism
  • Ferrous Compounds / metabolism
  • Ferrozine / pharmacology
  • Glycerol / chemistry
  • Glycerol / pharmacology*
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Osteogenesis / drug effects*
  • Phytic Acid / analogs & derivatives
  • Phytic Acid / chemistry
  • Phytic Acid / pharmacology*
  • Primary Cell Culture
  • RAW 264.7 Cells
  • Toxicity Tests, Subacute

Substances

  • Antioxidants
  • Cations, Divalent
  • Chelating Agents
  • Collagen Type I
  • Ferrous Compounds
  • Ferrozine
  • Phytic Acid
  • Alkaline Phosphatase
  • Glycerol
  • ferrous chloride
  • Calcium