{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:41:38Z","timestamp":1788968498373,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T00:00:00Z","timestamp":1354665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T00:00:00Z","timestamp":1354665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T00:00:00Z","timestamp":1354665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The concept of molecular hybridization led us to discover a novel series of coumarin\u2013dihydropyridine 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 picomolar concentrations. A series of other in vitro data strongly suggested compound 18 as the most promising bone anabolic agent, which was further evaluated for in vivo studies. From these studies compound 18 proved to be 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), and mineral apposition rate (MAR), improved the trabecular microarchitecture, and decreased bone turn over markers in an ovariectomized rodent model for postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1021\/jm301281e","type":"journal-article","created":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T11:28:22Z","timestamp":1354706902000},"page":"109-122","source":"Crossref","is-referenced-by-count":77,"title":["Discovery of Coumarin\u2013Dihydropyridine\nHybrids\nas Bone Anabolic Agents"],"prefix":"10.1021","volume":"56","author":[{"given":"Koneni V.","family":"Sashidhara","sequence":"first","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Medicinal and Process Chemistry Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Medicinal and Process Chemistry Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Khedgikar","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Endocrinology Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Endocrinology Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram K.","family":"Modukuri","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Medicinal and Process Chemistry Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdhesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Medicinal and Process Chemistry Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Gautam","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Endocrinology Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Singh","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Endocrinology Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramaniam","family":"Sridhar","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Technology (CSIR-IICT) Laboratory of X-ray Crystallography, , Hyderabad, 500 007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Trivedi","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute (CSIR-CDRI) Endocrinology Division, , Lucknow, 226 001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2012,12,5]]},"reference":[{"key":"2026081706075579100_cit1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1359\/JBMR.041114","article-title":"Drugs used to treat osteoporosis: the critical need\nfor a uniform nomenclature based on their action on bone remodeling","volume":"20","author":"Riggs","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"2026081706075579100_cit2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-4615-4217-9_4","article-title":"New concepts\nin the pathogenesis and treatment of osteoporosis","volume":"1","author":"Ershler","year":"2000","journal-title":"Front. Biomed."},{"key":"2026081706075579100_cit3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0014-2999(02)02659-6","article-title":"Incadronate inhibits osteoporosis\nin ovariectomized rats","volume":"457","author":"Kyoko","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"2026081706075579100_cit4a","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1359\/JBMR.0301220","article-title":"Adipogenic differentiation of human\nadult stem cells\nfrom bone marrow stroma (MSCs)","volume":"19","author":"Sekiya","year":"2004","journal-title":"J. Bone Miner.\nRes."},{"key":"2026081706075579100_cit4b","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1136\/jcp.55.9.693","article-title":"Adipocytic proportion\nof bone marrow is inversely related to bone formation in osteoporosis","volume":"55","author":"Verma","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"2026081706075579100_cit4c","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/8756-3282(87)90015-9","article-title":"Changes in trabecular\nbone, hematopoiesis and bone marrow vessels in aplastic anemia, primary\nosteoporosis, and old age: a comparative histomorphometric study","volume":"8","author":"Burkhardt","year":"1987","journal-title":"Bone"},{"key":"2026081706075579100_cit5a","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/jm980344o","article-title":"Emerging\ntherapies for the prevention or treatment\nof postmenopausal osteoporosis","volume":"42","author":"Sato","year":"1999","journal-title":"J. Med. Chem."},{"key":"2026081706075579100_cit5b","first-page":"623","article-title":"Role of adipocytokine\nin bone metabolism","volume":"18","author":"Ebina","year":"2008","journal-title":"Clin. 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Hypertens."},{"key":"2026081706075579100_cit8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejphar.2007.09.027","article-title":"Protective\neffects of amlodipine and lacidipine on ovariectomy-induced bone loss\nin rats","volume":"579","author":"Halici","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"2026081706075579100_cit9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejphar.2010.02.039","article-title":"Protective\neffect of amlodipine against\nosteoporosis in stroke-prone spontaneously hypertensive rats","volume":"635","author":"Ushijima","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"2026081706075579100_cit10a","volume-title":"Coumarins Biology,\nApplications and Mode of Action","author":"Kennedy","year":"1997"},{"key":"2026081706075579100_cit10b","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0306-3623(95)02112-4","article-title":"Pharmacological and\nbiochemical actions of simple coumarins: natural products with therapeutic\npotential","volume":"27","author":"Hoult","year":"1996","journal-title":"Gen. Pharmacol."},{"key":"2026081706075579100_cit11a","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1248\/bpb.25.738","article-title":"Effects of\nosthole on postmenopausal osteoporosis using ovariectomized rats.\nComparison to the effects of estradiol","volume":"25","author":"Li","year":"2002","journal-title":"Biol.\nPharm. Bull."},{"key":"2026081706075579100_cit11b","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ejphar.2007.10.013","article-title":"Enhancement of bone morphogenetic\nprotein-2 expression and bone formation by coumarin derivatives via\np38 and ERK-dependent pathway in osteoblasts","volume":"579","author":"Tang","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"2026081706075579100_cit11c","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.bbrc.2011.01.021","article-title":"Psoralen\nstimulates osteoblast differentiation through activation of BMP signalling","volume":"405","author":"Tang","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026081706075579100_cit11d","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000328776","article-title":"Osthole, a coumarin isolated from common Cnidium fruit,\nenhances the differentiation and maturation of osteoblasts in vitro","volume":"88","author":"Ming","year":"2011","journal-title":"Pharmacology"},{"key":"2026081706075579100_cit12a","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1016\/j.bmcl.2011.09.100","article-title":"Synthesis of novel\n3-carboxamide-benzocoumarin derivatives as orally active antithrombotic\nagents","volume":"21","author":"Sashidhara","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit12b","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1016\/j.bmcl.2011.09.053","article-title":"Discovery and synthesis of novel\nsubstituted benzocoumarins as orally active lipid modulating agents","volume":"21","author":"Sashidhara","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit12c","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.bmcl.2011.02.040","article-title":"Discovery\nand synthesis of novel 3-phenylcoumarin derivatives as antidepressant\nagents","volume":"21","author":"Sashidhara","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit12d","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1016\/j.bmcl.2010.05.023","article-title":"Novel coumarin derivatives\nas potential antidyslipidemic agents","volume":"20","author":"Sashidhara","year":"2010","journal-title":"Bioorg.\nMed. Chem. Lett."},{"key":"2026081706075579100_cit12e","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1016\/j.bmcl.2010.03.103","article-title":"Synthesis of novel\nbenzocoumarin derivatives as lipid lowering agents","volume":"20","author":"Sashidhara","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit12f","doi-asserted-by":"crossref","first-page":"6504","DOI":"10.1016\/j.bmcl.2010.09.055","article-title":"Synthesis and antihyperlipidemic activity of novel coumarin bisindole\nderivatives","volume":"20","author":"Sashidhara","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit12g","doi-asserted-by":"crossref","first-page":"7127","DOI":"10.1016\/j.bmcl.2010.09.040","article-title":"Neo-tanshinlactone inspired synthesis,\nin vitro evaluation of novel substituted benzocoumarin derivatives\nas potent anti-breast cancer agents","volume":"20","author":"Sashidhara","year":"2010","journal-title":"Bioorg.\nMed. Chem. Lett."},{"key":"2026081706075579100_cit13","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1016\/j.bmcl.2010.10.116","article-title":"Synthesis\nand in vitro evaluation of novel coumarin-chalcone hybrids as potential\nanticancer agents","volume":"20","author":"Sashidhara","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit14","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/cber.18810140214","article-title":"Condensationprodukteaus\naldehydammoniak und ketoniartigen verbindungen","volume":"14","author":"Hantzsch","year":"1881","journal-title":"Chem. Ber."},{"key":"2026081706075579100_cit15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mce.2008.02.027","article-title":"Kaempferol\nhas osteogenic effect in ovariectomized\nadult Sprague-Dawley rats","volume":"289","author":"Trivedi","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"2026081706075579100_cit16","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1016\/j.bmc.2010.05.015","article-title":"Synthesis\nand anti breast cancer activity of biphenyl\nbased chalcones","volume":"18","author":"Sharma","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"2026081706075579100_cit17","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1002\/jcp.22618","article-title":"Evidence of specific characteristics\nand osteogenic\npotentiality in bone cells from tibia","volume":"226","author":"Manferdini","year":"2011","journal-title":"J. Cell.\nPhysiol."},{"key":"2026081706075579100_cit18","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/jcb.22264","article-title":"Methoxylated\nisoflavones, cajanin and isoformononetin, have non-estrogenic bone\nforming effect via differential mitogen activated protein kinase (MAPK)\nsignaling","volume":"108","author":"Bhargavan","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"2026081706075579100_cit19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.mce.2009.01.011","article-title":"Effects of\nEgb 761 on bone mineral density, bone microstructure, and osteoblast\nfunction: possible roles of quercetin and kaempferol","volume":"302","author":"Trivedi","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"2026081706075579100_cit20","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.bone.2011.05.013","article-title":"MicroCT morphometry analysis of mouse cancellous bone:\nintra- and inter-system reproducibility","volume":"49","author":"Verdelis","year":"2011","journal-title":"Bone"},{"key":"2026081706075579100_cit21","first-page":"527","article-title":"Determinants\nof skeletal fragility and bone quality","volume":"2","author":"Turner","year":"2002","journal-title":"J. Musculoskeletal\nNeuronal Interact."},{"key":"2026081706075579100_cit22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s001980200000","article-title":"Biomechanics\nof bone: determinants of skeletal fragility and bone quality","volume":"13","author":"Turner","year":"2002","journal-title":"Osteoporosis Int."},{"key":"2026081706075579100_cit23","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/jbmr.434","article-title":"A novel quercetin analogue from a medicinal plant promotes\npeak bone mass achievement and bone healing after injury and exerts\nan anabolic effect on osteoporotic bone: the role of aryl hydrocarbon\nreceptor as a mediator of osteogenic action","volume":"26","author":"Sharan","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"2026081706075579100_cit24","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.bmcl.2011.12.036","article-title":"Constituents\nof Dalbergia sissoo Roxb. leaves with\nosteogenic activity","volume":"22","author":"Dixit","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026081706075579100_cit25","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1007\/s00198-010-1519-4","article-title":"A naturally\noccurring rare analog of quercetin promotes peak bone mass achievement\nand exerts anabolic effect on osteoporotic bone","volume":"22","author":"Siddiqui","year":"2011","journal-title":"Osteoporosis Int."},{"key":"2026081706075579100_cit26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ab.2004.02.002","article-title":"An alizarin red-based\nassay of mineralization by adherent cells in culture: comparison with\ncetylpyridinium chloride extraction","volume":"329","author":"Gregory","year":"2004","journal-title":"Anal. Biochem."},{"key":"2026081706075579100_cit27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/01495739708936692","article-title":"Quantification\nof bone microarchitecture with the structure\nmodel index","volume":"1","author":"Hildebrand","year":"1997","journal-title":"Comput. Methods Biomech. Biomed.\nEngin."},{"key":"2026081706075579100_cit28","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/j.1476-5381.2011.01637.x","article-title":"A naturally\noccurring naringenin derivative exerts potent bone anabolic effects\nby mimicking oestrogen action on osteoblasts","volume":"165","author":"Swarnkar","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"2026081706075579100_cit29","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.phymed.2012.07.005","article-title":"EGb 761 promotes osteoblastogenesis,\nlowers bone marrow adipogenesis and atherosclerotic plaque formation","volume":"19","author":"Gautam","year":"2012","journal-title":"Phytomedicine"},{"key":"2026081706075579100_cit30","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1097\/GME.0b013e318256b6ae","article-title":"A standardized phytopreparation\nfrom an Indian medicinal plant (Dalbergia sissoo) has antiresorptive and bone-forming effects on a postmenopausal\nosteoporosis model of rat","volume":"19","author":"Khedgikar","year":"2012","journal-title":"Menopause"},{"key":"2026081706075579100_cit31","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ejpb.2012.08.001","article-title":"In vivo efficacy\nstudies of layer-by-layer nano-matrix bearing kaempferol for the conditions\nof osteoporosis: a study in ovariectomized rat model","volume":"82","author":"Kumar","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jm301281e","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article-pdf\/56\/1\/109\/16876123\/jm301281e.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article-pdf\/56\/1\/109\/16876123\/jm301281e.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:14:24Z","timestamp":1786961664000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article\/56\/1\/109\/1590232\/Discovery-of-Coumarin-Dihydropyridine-Hybrids-as"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,5]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,12,5]]},"published-print":{"date-parts":[[2013,1,10]]}},"URL":"https:\/\/doi.org\/10.1021\/jm301281e","relation":{},"ISSN":["0022-2623","1520-4804"],"issn-type":[{"value":"0022-2623","type":"print"},{"value":"1520-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,5]]}}}