{"created":"2023-05-15T16:49:47.946091+00:00","id":27404,"links":{},"metadata":{"_buckets":{"deposit":"09472329-d52b-4b96-a22e-9229aaca7c6b"},"_deposit":{"created_by":6,"id":"27404","owners":[6],"pid":{"revision_id":0,"type":"depid","value":"27404"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00027404","sets":["10:11"]},"author_link":["121903","121904","121909","121910","121911","121905","121907","121908","121902","121906"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-03-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"219","bibliographicPageStart":"211","bibliographicVolumeNumber":"70","bibliographic_titles":[{"bibliographic_title":"Chemical and Pharmaceutical Bulletin"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Prion diseases are fatal neurodegenerative diseases characterized by the deposition of abnormal prion protein aggregates (PrPSc) in the brain. In this study, we developed hydroxyethylamino-substituted styrylchromone (SC) and 2-(2-(pyridin-3-yl)vinyl)-4H-chromen-4-one (VPC) derivatives for single-photon emission computed tomography (SPECT) imaging of PrPSc deposits in the brain. The binding affinity of these compounds was evaluated using recombinant mouse prion protein (rMoPrP) aggregates, which resulted in the inhibition constant (Ki) value of 61.5 and 88.0 nM for hydroxyethyl derivative, (E)-2-(4-((2-hydroxyethyl)amino)styryl)-6-iodo-4H-chromen-4-one (SC-NHEtOH) and (E)-2-(4-((2-hydroxyethyl)(methyl)amino)styryl)-6-iodo-4H-chromen-4-one (SC-NMeEtOH), respectively. However, none of the VPC derivatives showed binding affinity for the rMoPrP aggregates. Fluorescent imaging demonstrated that the accumulation pattern of SC-NHEtOH matched with the presence of PrPSc in the brain slices from mouse-adapted bovine spongiform encephalopathy-infected mice. A biodistribution study of normal mice indicated low initial brain uptake of [125I]SC-NHEtOH (0.88% injected dose/g (% ID/g) at 2 min) despite favorable washout from the brain (0.26% ID/g, at 180 min) was displayed. [125I]SC-NHEtOH exhibited binding affinities to both artificial prion aggregates as well as prion deposits in the brain. However, significant improvement in the binding affinity for PrPSc and blood–brain barrier permeability is necessary for the development of successful in vivo imaging probes for the detection of cerebral PrPSc in the brain.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Chemical and Pharmaceutical Bulletin, 70(3), pp. 211-219; 2022","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Pharmaceutical Society of Japan"}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1248/cpb.c21-00902","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022 The Pharmaceutical Society of Japan"}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0009-2363","subitem_source_identifier_type":"ISSN"}]},"item_2_text_62":{"attribute_name":"出版者別言語","attribute_value_mlt":[{"subitem_text_value":"日本薬学会"}]},"item_2_version_type_16":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nakaie, Mari"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Katayama, Fumihiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nakagaki, Takehiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kawasaki, Masao"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yoshida, Sakura"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Toriba, Akira"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ogawa, Kazuma"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nishida, Noriyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nakayama, Morio"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Fuchigami, Takeshi"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-19"}],"displaytype":"detail","filename":"CPB70_211.pdf","filesize":[{"value":"2.2 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"CPB70_211.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/27404/files/CPB70_211.pdf"},"version_id":"f682e48f-4be5-4b62-91d0-0d93f655b61c"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"prion disease","subitem_subject_scheme":"Other"},{"subitem_subject":"scrapie prion protein (PrPSc)","subitem_subject_scheme":"Other"},{"subitem_subject":"2-vinyl chromone","subitem_subject_scheme":"Other"},{"subitem_subject":"single-photon emission computed tomography (SPECT)","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits"}]},"item_type_id":"2","owner":"6","path":["11"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-05-19"},"publish_date":"2022-05-19","publish_status":"0","recid":"27404","relation_version_is_last":true,"title":["Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits"],"weko_creator_id":"6","weko_shared_id":-1},"updated":"2023-05-15T19:46:23.660562+00:00"}