Defining Key Structural Determinants for the Pro-osteogenic Activity of Flavonoids
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- 作者：Stephen Swioklo ; Kimberly A. Watson ; Elizabeth M. Williamson ; Jonathan A. Farrimond ; Sophie E. Putnam ; Katrina A. Bicknell
- 刊名：Journal of Natural Products
- 出版年：2015
- 出版时间：November 25, 2015
- 年：2015
- 卷：78
- 期：11
- 页码：2598-2608
- 全文大小：677K
- ISSN：1520-6025
文摘
Epidemiological studies suggest that fruits and vegetables may play a role in promoting bone growth and preventing age-related bone loss, attributable, at least in part, to phytochemicals such as flavonoids stimulating osteoblastogenesis. Through systematically screening the effect of flavonoids on the osteogenic differentiation of human mesenchymal stem cells in vitro and correlating activity with chemical structure using comparative molecular field analysis, we have successfully identified important structural features that relate to their activity, as well as reliably predicted the activity of compounds with unknown activity. Contour maps emphasized the importance of electronegativity, steric bulk, and a 2-C鈥?-C double bond at the flavonoid C-ring, as well as overall electropositivity and reduced steric bulk at the flavonoid B-ring. These results support a role for certain flavonoids in promoting osteogenic differentiation, thus their potential for preventing skeletal deterioration, as well as providing a foundation for the lead optimization of novel bone anabolics.