title: One step synthesis of 2-hydroxymethylisoflavone and their osteogenic activity.
abstract: An efficient one step synthesis of new 2-hydroxymethylisoflavone is reported. A series of deoxybenzoin was subjected to cyclization with glyoxal in the presence of basic condition (KOH/EtOH) to afford the 2-hydroxymethyl isoflavone. The structures of compounds 5a-g were confirmed by NMR experiments including (1)H, (13)C, HMBC, HSQC and COSY. These compounds were assessed for stimulation of osteoblast function using primary culture of rat calvarial osteoblasts in vitro. Compounds 5a, 5d, 5f and 5g were potent in stimulating differentiation of osteoblasts as assessed by measuring alkaline phosphatase (ALP) activity. Besides, effect of these analogs was also seen on the transcript levels of osteogenic genes like Runx-2, osteocalcin and Bone morphogenetic protein-2 (BMP-2), involved in osteoblast differentiation and mineralization. Based on quantitative PCR data, compound 5f was found to be the potent followed by 5d. Compound 5f robustly increased the mRNA levels of Runx-2 (8.0 fold), BMP-2 (∼2 fold) and osteocalcin (∼2.0 fold) in osteoblasts. Collectively, we demonstrate osteogenic activity of the novel 2-hydroxymethyl isoflavones with 5f having the most potent activity.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow, UP, India.
authors.forename: Manmeet
authors.initials: M
authors.lastname: Kumar
authors.forename: Preeti
authors.initials: P
authors.lastname: Rawat
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.forename: Anuj Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats
chemical_list: D007529:Isoflavones