title: Defining Key Structural Determinants for the Pro-osteogenic Activity of Flavonoids.
abstract: 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-3-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.
authors.affiliation: Reading School of Pharmacy, University of Reading , Whiteknights, Reading RG6 6UB, U.K.
authors.forename: Stephen
authors.initials: S
authors.lastname: Swioklo
authors.affiliation: School of Biological Sciences, University of Reading , Whiteknights, Reading RG6 6AJ, U.K.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Watson
authors.affiliation: Reading School of Pharmacy, University of Reading , Whiteknights, Reading RG6 6UB, U.K.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Williamson
authors.affiliation: GlaxoSmithKline, GSK House , 980 Great West Road, Brentford, Middlesex TW8 9GS, U.K.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Farrimond
authors.affiliation: GlaxoSmithKline, GSK House , 980 Great West Road, Brentford, Middlesex TW8 9GS, U.K.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Putnam
authors.affiliation: Reading School of Pharmacy, University of Reading , Whiteknights, Reading RG6 6UB, U.K.
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Bicknell
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D015394:Molecular Structure; D010012:Osteogenesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids