title: Synthetic analogs of daidzein, having more potent osteoblast stimulating effect.
abstract: A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute (Council of Scientific and Industrial Research), Lucknow 226 001, India.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Yadav
authors.forename: Abnish K
authors.initials: AK
authors.lastname: Gautam
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.forename: Kamini
authors.initials: K
authors.lastname: Srivastava
authors.forename: Mahendra
authors.initials: M
authors.lastname: Sahai
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D048789:Phytoestrogens / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012886:Skull / Q000166:cytology
chemical_list: D055396:Bone Morphogenetic Protein 2; D007529:Isoflavones; D048789:Phytoestrogens; D012333:RNA, Messenger; D015675:Osteocalcin; C004742:daidzein