title: Differentiation of skeletal osteogenic progenitor cells to osteoblasts with 3,4-diarylbenzopyran based amide derivatives: Novel osteogenic agents.
abstract: A series of 3,4-diarylbenzopyran based amide derivatives was synthesized and evaluated for osteogenic activity in in vitro and in vivo models of osteoporosis. Compounds 17a, 21b-c and 22a-b showed significant osteogenic activity in osteoblast differentiation assay. Among the synthesized compounds, 22b was identified as lead molecule which showed significant osteogenic activity at 1 pM concentration in osteoblast differentiation assay and at 1 mg kg(-1) body weight dose in estrogen deficient balb/c mice model. In vitro bone mineralization and expression of osteogenic marker genes viz BMP-2, RUNX-2, OCN, and collagen type 1 further confirmed the osteogenic potential of 22b. Gene expression study for estrogen receptor α and β (ER-α and ER-β) in mouse calvarial osteoblasts (MCOs) unveiled that possibly 22b exerted osteogenic efficacy via activation of Estrogen receptor-β preferentially. In vivo pharmacokinetic, estrogenicity and acute toxicity studies of 22b showed that it had good bioavailability and was devoid of uterine estrogenicity at 1 mg kg(-1) and inherent toxicity up to 1000 mg kg(-1) body weight dose respectively.
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO. CIMAP, Kukrail Road, Lucknow, 226015, India. Electronic address: atisky2001@yahoo.co.in.
authors.forename: Atul
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO. CIMAP, Kukrail Road, Lucknow, 226015, India.
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India.
authors.forename: Aijaz A
authors.initials: AA
authors.lastname: John
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO. CIMAP, Kukrail Road, Lucknow, 226015, India.
authors.forename: Eram
authors.initials: E
authors.lastname: Sultan
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO. CIMAP, Kukrail Road, Lucknow, 226015, India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chanda
authors.affiliation: Division of Pharmacokinetics and Metabolism, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India; Department of Zoology, HNB Garhwal Central University, Badshahi Thaul Campus, Tehri Garhwal 249 199, Uttarakhand, India.
authors.forename: Naresh Kumar
authors.initials: NK
authors.lastname: Agarwal
authors.affiliation: Division of Pharmacokinetics and Metabolism, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India; Department of Zoology, HNB Garhwal Central University, Badshahi Thaul Campus, Tehri Garhwal 249 199, Uttarakhand, India.
authors.lastname: Alauddin
authors.affiliation: Division of Pharmacokinetics and Metabolism, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India.
authors.lastname: Wahajuddin
authors.affiliation: National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.
authors.forename: S
authors.initials: S
authors.lastname: Prabhaker
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, PO. CIMAP, Kukrail Road, Lucknow, 226015, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Verma
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002454:Cell Differentiation / Q000187:drug effects*; D047629:Estrogen Receptor beta / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced; D013234:Stem Cells / Q000166:cytology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001578:Benzopyrans; D047629:Estrogen Receptor beta
keywords: Antiosteoporotic; Benzopyran; Estrogen; Isoflavone; Osteogenic