Please use this identifier to cite or link to this item:
|Title:||Discovery of Coumarin-Dihydropyridine Hybrids as Bone Anabolic Agents|
|Authors:||Sashidhara, K V;Kumar, Manoj;Khedgikar, Vikram;Kushwaha, Priyanka;Modukuri, R K;Kumar, Abdhesh;Gautam, Jyoti;Singh, Divya;Sridhar, Balasubramaniam;Trivedi, Ritu|
|subject:||Coumarin-Dihydropyridine Hybrids;Osteoblastic bone;RUNX2;BMP-2;ColI;BFR;MAR|
|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.|
|Standard no:||Journal of Medicinal Chemistry. 2013, 56(1), 109-22|
|Appears in Collections:||Medicinal and Process Chemistry|
Files in This Item:
Click on the URI links for accessing contents.
Items in HannanDL are protected by copyright, with all rights reserved, unless otherwise indicated.