Synthesis and evaluation of organosilicon inhibitors of active purine transport in human osteoblasts

Chembiochem. 2002 Apr 2;3(4):341-7. doi: 10.1002/1439-7633(20020402)3:4<341::AID-CBIC341>3.0.CO;2-B.

Abstract

In the search for new compounds that might, once incorporated into biomaterials, stimulate the natural processes of bone regeneration, a new series of silicon-containing alkyl nucleobase analogues has been synthesized. An active hypoxanthine transport process in human osteoblasts was demonstrated, with an apparent Michaelis constant of 2.3 microM and a maximum possible rate of 0.47 pmol s(-1) x 10(6) cell. The synthesized analogues were tested for toxicity in human osteoblasts. Nontoxic analogues were tested in competition transport studies with [(14)C]hypoxanthine. Two of them were found to inhibit the active transport of hypoxanthine in human osteoblasts, with IC(50) values of 6.5 and 11.6 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biocompatible Materials / adverse effects
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry*
  • Biological Transport, Active / drug effects
  • Cells, Cultured
  • Humans
  • Middle Aged
  • Organosilicon Compounds / adverse effects
  • Organosilicon Compounds / chemical synthesis
  • Organosilicon Compounds / chemistry*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Purines / metabolism*

Substances

  • Biocompatible Materials
  • Organosilicon Compounds
  • Purines