title: 3-Piperidylethoxypterocarpan: A potential bone anabolic agent that improves bone quality and restores trabecular micro-architecture in ovariectomized osteopenic rats.
abstract: A series of new 6H-benzofuro[3, 2-c]chromenes (BFC, pterocarpans) with structure-activity relationships were investigated for their potential use in osteoporosis treatment. One of the BFCs 3-piperidylethoxypterocarpan 20 promotes osteoblast differentiation and mineralization at a dose as low as 1 pM via activation of ER/P38MAPK/BMP-2 pathway. When evaluated for in-vivo osteogenic activity in female Sprague-Dawley rats, BFC 20 increased bone mineral density and new bone formation, compared with control at 1.0 and 10.0 mg/kg/body weight by oral gavage for 30 days. The compound was devoid of any uterotrophic effect and led to the new bone formation in adult ovariectomized osteopenic rats. BFC 20 compound also inhibited bone resorption by reducing Ovx induced increase in urinary CTx, thus exhibiting both bone anabolic and anti-catabolic action. Finally, BFC 20 treatment to Ovx rats led to improved trabecular microarchitectural restoration and exhibited therapeutic potential as a dual acting anti-osteoporotic agent for the management of osteoporosis.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Raghuvanshi
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Abdul M
authors.initials: AM
authors.lastname: Tyagi
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Awasthi
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Purohit
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Mohd Nizam
authors.initials: MN
authors.lastname: Mansoori
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kamini
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Abnish K
authors.initials: AK
authors.lastname: Gautam
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: divya_singh@cdri.res.in.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: atul_goel@cdri.res.in.
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D045930:Anabolic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D000071556:Cancellous Bone / Q000187:drug effects / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D036343:Pterocarpans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000624689:3-piperidylethoxypterocarpan; D045930:Anabolic Agents; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D010880:Piperidines; D036343:Pterocarpans; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000469:Alkaline Phosphatase
keywords: BMP-2 activator; Benzofurochromene; Bone anabolic agent; Osteoporosis; Ovariectomized