Nitric Oxide-Donating Genistein Prodrug: Design, Synthesis, and Bioactivity on MC3T3-E1 Cells

• Main Authors: Jiepin Wang, Fujun Shang, Ru Jiang, Li Liu, Siwang Wang, Jin Hou, Menglei Huan, Qibing Mei
• Format: Article
• Language: English
• Published: Elsevier 2007-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319342811

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. Keywords:: postmenopausal osteoporosis, nitric oxide (NO)-releasing prodrug, synthesis, MC3T3-E1 cell, bioactivity