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Synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2009 Sep; Vol. 44 (9), pp. 3621-6. Date of Electronic Publication: 2009 Mar 04. - Publication Year :
- 2009
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Abstract
- We report herein the synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives. The results indicated that 3-(3,4-dimethoxyphenyl)-7-(oxiran-2-ylmethoxy)-4H-chromen-4-one (4) and 3-{4-[3-(cyclohexylamino)-2-hydroxypropoxy]phenyl}-7-methoxy-4H-chromen-4-one (5a) exhibited significant inhibitory effects on osteoclast activity (TRAP activity in RAW 264.7 with an ED(50) of 0.56 and 2.28 microM respectively). Both compounds have also exhibited very strong osteogenic effects, approximately a 10-fold effect of Ipriflavone on mineralization of osteoblasts (MC3T3E1 cells, a preosteoblast cell line derived from calvaria of C57BL/6 mice). Results indicated the potency on enhancing mineralization in D1 cells (a bone marrow mesenchymal cell line derived from BALB/c mice) decreased in an order 4>Ipriflavone>5a. However, the potency on enhancing mineralization in human adipose tissue derived stem cells (hADSCs) decreased in an order 5a>4>Raloxifene>Ipriflavone. Compound 5a has been found to be non-cytotoxic and especially active in the enhancement of mineralization in human adipose tissue derived stem cells. Therefore, 5a was selected as a potential lead for further structural optimization.
- Subjects :
- Adipose Tissue cytology
Animals
Bone Marrow Cells cytology
Bone Marrow Cells drug effects
Calcification, Physiologic drug effects
Cell Differentiation drug effects
Cell Line
Cell Survival drug effects
Cells, Cultured
Humans
Isoflavones chemical synthesis
Isoflavones toxicity
Mesoderm cytology
Mice
Mice, Inbred C57BL
Osteoblasts cytology
Osteoblasts drug effects
Stem Cells cytology
Stem Cells drug effects
Isoflavones chemistry
Isoflavones pharmacology
Osteogenesis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 44
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19339083
- Full Text :
- https://doi.org/10.1016/j.ejmech.2009.02.025