Synthesis and evaluation of organosilicon inhibitors of active purine transport in human osteoblasts.
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.
Ciro
Sol
S
INSERM U 443, Université Victor Segalen-Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Rubio
Cyril
C
Estieu-Gionnet
Karine
K
Latxague
Laurent
L
Déléris
Gérard
G
Bareille
Reine
R
Amédée
Joëlle
J
Baquey
Charles
C
D000328:Adult; D000368:Aged; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008875:Middle Aged; D017646:Organosilicon Compounds / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*
D001672:Biocompatible Materials; D017646:Organosilicon Compounds; D011687:Purines