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Design and synthesis of dalbergin analogues and evaluation of anti-osteoporotic activity
Padam Kumar1, Priyanka Kushwaha2, Naseer Ahmad3
1Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Abstract:
The chemical modifications of the hydroxyl group of dalbergin have been described via the introduction of cyclic amine, ester and amide groups. Among the twenty-three prepared novel analogues of dalbergin, compound 4d (EC50 2.3μM) showed significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells in vitro. Compound 4d, at a dose of 1.0mg/kg body weight exhibited the significant osteoprotective effect. It showed a significant increase in osteogenic gene expression RunX2 (∼4fold), ALP (∼5fold), OCN (∼4fold) and COL1 (∼4fold) as compared to control group at the same dose in vivo assay.
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