Design and and synthesis of dalbergin analogues and evaluation of anti-osteoporotic activity

摘要

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 2.3 mu M) showed significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells in vitro. Compound 4d, at a dose of 1.0 mg/kg body weight exhibited the significant osteoprotective effect. It showed a significant increase in osteogenic gene expression RunX2 (similar to 4fold), ALP (similar to 5fold), OCN (similar to 4fold) and COL1 (similar to 4fold) as compared to control group at the same dose in vivo assay. (C) 2017 Elsevier Ltd. All rights reserved.