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(3R,5S,7as)-(3,5-bis(4-Fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol: A Novel Neuroprotective Agent
dc.contributor.author | Desino, Kelly Elizabeth | |
dc.contributor.author | Ansar, Sabah | |
dc.contributor.author | Georg, Gunda I. | |
dc.contributor.author | Himes, Richard H. | |
dc.contributor.author | Michaelis, Mary Lou | |
dc.contributor.author | Powell, Douglas R. | |
dc.contributor.author | Reiff, Emily A. | |
dc.contributor.author | Telikepalli, Hanumaiah | |
dc.contributor.author | Audus, Kenneth L. | |
dc.date.accessioned | 2017-04-06T15:45:54Z | |
dc.date.available | 2017-04-06T15:45:54Z | |
dc.date.issued | 2009-12-10 | |
dc.identifier.citation | Desino, K. E., Ansar, S., Georg, G. I., Himes, R. H., Michaelis, M. L., Powell, D. R., … Audus, K. L. (2009). (3R,5S,7as)-(3,5-bis(4-Fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol: A Novel Neuroprotective Agent. Journal of Medicinal Chemistry, 52(23), 7537–7543. http://doi.org/10.1021/jm900254k | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23580 | |
dc.description.abstract | Compounds that interact with microtubules, such as paclitaxel, have been shown to possess protective properties against β-amyloid (Aβ)-induced neurodegeneration associated with Alzheimer's disease. In this work, the novel agent (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol was investigated for effectiveness in protecting neurons against several toxic stimuli and its interaction with the microtubule network. Exposure of neuronal cultures to Aβ peptide in the presence of 5 nM (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol resulted in a 50% increase in survival. Neuronal cultures treated with other toxic stimuli such as staurosporine, thapsigargin, paraquat and H2O2 showed significantly enhanced survival in the presence of (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol. Microtubule binding and tubulin assembly studies revealed differences compared to paclitaxel, but confirmed the interaction of (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol with microtubules. Furthermore, in vitro studies using bovine brain microvessel endothelial cells experiments suggest that (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol can readily cross the blood-brain barrier in a passive manner. | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm900254k. | en_US |
dc.title | (3R,5S,7as)-(3,5-bis(4-Fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol: A Novel Neuroprotective Agent | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Desino, Kelly E. | |
kusw.kuauthor | Ansar, Sabah | |
kusw.kuauthor | Georg, Gunda I. | |
kusw.kuauthor | Himes, Richard H. | |
kusw.kuauthor | Michaelis, Mary Lou | |
kusw.kuauthor | Powell, Douglas R. | |
kusw.kuauthor | Reiff, Emily A. | |
kusw.kuauthor | Telikepalli, Hanumaiah | |
kusw.kuauthor | Audus, Kenneth L. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1021/jm900254k | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-7133-468X | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |