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Synthesis of benzofuran derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase: effects on cell toxicity and osteoblast-induced mineralization
被引:10
作者:

Marques, Stephanie
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Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France

Buchet, Rene
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Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Org & Dynam Membranes Biol, UMR CNRS 5246, F-69622 Villeurbanne, France Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France

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Lemaire, Marc
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Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France

Mebarek, Saida
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Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Org & Dynam Membranes Biol, UMR CNRS 5246, F-69622 Villeurbanne, France Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France
机构:
[1] Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Catalyse Synth Environm, UMR CNRS 5246, F-69622 Villeurbanne, France
[2] Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Equipe Org & Dynam Membranes Biol, UMR CNRS 5246, F-69622 Villeurbanne, France
[3] Inst Natl Sci Appl INSA Lyon, Inst Chim & Biochim Mol & Supramol, Equipe Chim Organ & Bioorgan, F-69621 Villeurbanne, France
关键词:
Alkaline phosphatase;
Mineralization;
Benzofuran derivatives;
Calcification disease;
Inhibitors;
CALCIFICATION;
LOCALIZATION;
DESIGN;
BONE;
D O I:
10.1016/j.bmcl.2016.01.061
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
Tissue-nonspecific alkaline phosphatase (TNAP) by hydrolyzing pyrophosphate, an inhibitor of apatite formation, promotes extracellular matrix calcification during bone formation and growth, as well as during ectopic calcification under pathological conditions. TNAP is a target for the treatment of soft tissue pathological ossification. We synthesized a series of benzofuran derivatives. Among these, SMA14, displayed TNAP activity better than levamisole. SMA14 was found to be not toxic at doses of up to 40 mu M in osteoblast-like Saos-2 cells and primary osteoblasts. As probed by Alizarin Red staining, this compound inhibited mineral formation in murine primary osteoblast and in osteoblast-like Saos-2 cells. (C) 2016 Elsevier Ltd. All rights reserved.
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页码:1457 / 1459
页数:3
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