97846-18-9Relevant academic research and scientific papers
Design, synthesis, and osteogenic activity of daidzein analogs on human mesenchymal stem cells
Strong, Amy L.,Jiang, Quan,Zhang, Qiang,Zheng, Shilong,Boue, Stephen M.,Elliott, Steven,Burow, Matthew E.,Bunnell, Bruce A.,Wang, Guangdi
, p. 143 - 148 (2014/03/21)
Osteoporosis is caused by an overstimulation of osteoclast activity and the destruction of the bone extracellular matrix. Without the normal architecture, osteoblast cells are unable to rebuild phenotypically normal bone. Hormone replacement therapy with estrogen has been effective in increasing osteoblast activity but also has resulted in the increased incidence of breast and uterine cancer. In this study we designed and synthesized a series of daidzein analogs to investigate their osteogenic induction potentials. Human bone marrow derived mesenchymal stem cells (MSCs) from three different donors were treated with daidzein analogs and demonstrated enhanced osteogenesis when compared to daidzein treatment. The enhanced osteogenic potential of these daidzein analogs resulted in increased osterix (Sp7), alkaline phosphatase (ALP), osteopontin (OPN), and insulin-like growth factor 1 (IGF-1), which are osteogenic transcription factors that regulate the maturation of osteogenic progenitor cells into mature osteoblast cells.
Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells
Jiang, Quan,Payton-Stewart, Florastina,Elliott, Steven,Driver, Jennifer,Rhodes, Lyndsay V.,Zhang, Qiang,Zheng, Shilong,Bhatnagar, Deepak,Boue, Stephen M.,Collins-Burow, Bridgette M.,Sridhar, Jayalakshmi,Stevens, Cheryl,McLachlan, John A.,Wiese, Thomas E.,Burow, Matthew E.,Wang, Guangdi
experimental part, p. 6153 - 6163 (2010/11/02)
Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7-hydroxyl hydrogen. To test the effect of such structural modifications on the hormonal activities of the resulting compounds, a series of daidzein analogues have been designed and synthesized. When MCF-7 cells were treated with the analogues, those resulting from hydrogen substitution by isopropyl (3d), isobutyl (3f), cyclopentyl (3g), and pyrano- (2) inhibited cell proliferation, estrogen-induced transcriptional activity, and estrogen receptor (ER) regulated progesterone receptor (PgR) gene expression. However, methyl (3a) and ethyl (3b) substitutions of the hydroxyl proton only led to moderate reduction of the estrogenic activities. These results demonstrated the structural requirements for the transformation of daidzein from an ER agonist to an antagonist. The most effective analogue, 2, was found to reduce in vivo estrogen stimulated MCF-7 cell tumorigenesis using a xenograft mouse model.
Characterization of cytochrome P450s mediating ipriflavone metabolism in human liver microsomes
Moon,Kim,Ji,Kim,Chae,Chae,Lee
, p. 246 - 259 (2008/09/17)
Ipriflavone, a synthetic flavonoid for the prevention and treatment of osteoporosis, has been reported to be extensively metabolized in man to seven metabolites (M1-M7). This study was performed to characterize the human liver cytochrome P450s (CYP) responsible for the metabolism of ipriflavone. Hydroxylation at the β-ring to M3, O-dealkylation to M1 and oxidation at isopropyl group to M4 and M5 are major pathways for ipriflavone metabolism in three different human liver microsome preparations. The specific CYPs responsible for ipriflavone oxidation to the active metabolites, M1, M3, M4 and M5 were identified using a combination of correlation analysis, immuno-inhibition, chemical inhibition in human liver microsomes and metabolism by expressed recombinant CYP enzymes. The inhibitory potencies of ipriflavone and its five metabolites, M1-M5 on seven clinically important CYPs were investigated in human liver microsomes. Our results demonstrate that CYP3A4 plays the major role in O-dealkylation of ipriflavone to M1 and CYP1A2 plays a dominant role in the formation of M3, M4 and M5. Ipriflavone and/or its five metabolites were found to inhibit potently the metabolism of CYPs 1A2, 2C8, 2C9 and 2C19 substrates.
Synthesis of potential antidipsotropic isoflavones: Inhibitors of the mitochondrial monoamine oxidase - Aldehyde dehydrogenase pathway
Gao,Li,Ming Keung
, p. 3320 - 3328 (2007/10/03)
Recently we have shown that daidzin, the major active principle of an ancient herbal treatment for quot;alcohol addictionquot; suppresses ethanol intake in alcohol-preferring laboratory animals. Further, we have identified the monoamine oxidase (MAO) - aldehyde dehydrogenase (ALDH-2) pathway of the mitochondria as the potential site of action of daidzin. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also inhibit MAO exhibit little, if any, antidipsotropic activity. Therefore, in the design and synthesis of more potent antidipsotropic analogues, structural features important for the inhibition of both ALDH-2 and MAO must be taken into consideration. To gain further information on the structure-activity relationships at the inhibitor binding sites of ALDH-2 and MAO, we prepared 44 analogues of daidzin and determined their potencies for ALDH-2 and MAO inhibition. Results indicate that a sufficient set of criteria for a potent antidipsotropic analogue is an isoflavone with a free 4′-OH function and a straight-chain alkyl substituent at the 7 position that has a terminal polar function such as -OH, -COOH, or -NH2. The preferable chain lengths for the 7-O-ω-hydroxy, 7-O-ω-carboxy, and 7-O-ω-amino subsitutents are 2 ≤ n ≤ 6, 5 ≤ n ≤ 10, and n ≥ 4, respectively. Analogues that meet these criteria have increased potency for ALDH-2 inhibition and/or decreased potency for MAO inhibition and therefore are likely to be potent antidipsotropic agents.
