Discovery of Coumarin-Dihydropyridine Hybrids as Bone Anabolic Agents
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Sashidhara, K V
Kumar, Manoj Khedgikar, Vikram Kushwaha, Priyanka Modukuri, R K Kumar, Abdhesh Gautam, Jyoti Singh, Divya Sridhar, Balasubramaniam Trivedi, Ritu |
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| Date |
2013-03-07T10:29:42Z
2013-03-07T10:29:42Z 2012 |
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| Identifier |
Journal of Medicinal Chemistry. 2013, 56(1), 109-22
http://hdl.handle.net/123456789/1023 |
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| Description |
The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds 10, 14, 18, and 22 showed significant activity at pM concentrations. A series of other in vitro data strongly suggested compound 18 as most promising bone anabolic agent, which was further evaluated for in vivo studies. From these studies compound 18 proved useful, which at low oral dose of 1 mg/kg/day body weight, increased bone mass density and volume, expression of osteogenic genes (RUNX2, BMP-2 and ColI), bone formation rate (BFR), mineral apposition rate (MAR), improved the trabecular microarchitecture and decreased bone turn over markers in an ovariectomized rodent model for postmenopausal osteoporosis.
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4383343 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Communication No. 8367
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| Subject |
Coumarin-Dihydropyridine Hybrids
Osteoblastic bone RUNX2 BMP-2 ColI BFR MAR |
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| Title |
Discovery of Coumarin-Dihydropyridine Hybrids as Bone Anabolic Agents
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| Type |
Article
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