RRC ID 10995
著者 Wang J, Shang F, Jiang R, Liu L, Wang S, Hou J, Huan M, Mei Q.
タイトル Nitric oxide-donating genistein prodrug: design, synthesis, and bioactivity on MC3T3-E1 cells.
ジャーナル J Pharmacol Sci
Abstract To find a more potent alternative with less estrogen-related side effects for hormone replacement therapy, we designed and synthesized a nitric oxide (NO)-releasing prodrug of genistein, named NO-donating genistein (NO-G). The characteristics of NO-G were determined by melting point, NMR spectroscopy, and mass spectrometric analysis. HPLC has been used to test the new prodrug's stability. The releasing capacity of NO-G was tested by Griess reagent in vitro. The bioactivities of NO-G on proliferation, differentiation, and mineralization of the osteoblastic cell line MC3T3-E1 were determined by MTT assay, flow cytometric analysis, measurement of the alkaline phosphatase (ALP) activity and the secreted osteocalcin (OCN), and Alizarin Red-S staining. The product showed 1H NMR spectra and relative molecular mass in agreement with the designed structure, and it was stable in buffer solution. NO-G continually released low level NO within 5 h in MC3T3-E1 cells. NO-G caused a significant elevation of cell growth, ALP activity, and OCN secretion in both dose- and time-dependent manner. Furthermore, the Alizarin Red-S staining showed that NO-G promoted mineralization of MC3T3-E1 cells. These effects were all significantly greater than those of its parent drugs. The results suggested that NO-G might be a novel drug for the treatment of postmenopausal osteoporosis.
巻・号 104(1)
ページ 82-9
公開日 2007-5-1
DOI 10.1254/jphs.fp0061549
PII JST.JSTAGE/jphs/FP0061549
PMID 17510526
MeSH 3T3 Cells Alkaline Phosphatase / metabolism Animals Butyrates / chemistry Cell Proliferation / drug effects* Chromatography, High Pressure Liquid Dose-Response Relationship, Drug Drug Design Drug Stability Flow Cytometry Genistein / analogs & derivatives* Genistein / chemistry Genistein / pharmacology* Magnetic Resonance Spectroscopy Mass Spectrometry Mice Molecular Structure Nitrates / chemistry* Nitric Oxide / metabolism Nitric Oxide Donors / chemistry Nitric Oxide Donors / pharmacology* Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism Osteocalcin / metabolism Phytoestrogens / chemistry Phytoestrogens / pharmacology Prodrugs / chemistry Prodrugs / pharmacology* S Phase / drug effects Time Factors
IF 2.835
引用数 13
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)