{"created":"2023-05-15T16:50:10.915440+00:00","id":27934,"links":{},"metadata":{"_buckets":{"deposit":"cfa14838-b9e5-4cef-86cc-338b4cb8f269"},"_deposit":{"created_by":6,"id":"27934","owners":[6],"pid":{"revision_id":0,"type":"depid","value":"27934"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00027934","sets":["35:36"]},"author_link":["124587","124590","124592","124585","124586","124593","124589","124588","124591"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2023-02-22","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"e01428-22","bibliographic_titles":[{"bibliographic_title":"Antimicrobial Agents and Chemotherapy"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Ascofuranone (AF), a meroterpenoid isolated from various filamentous fungi, including Acremonium egyptiacum, has been reported as a potential lead candidate for drug development against parasites and cancer. In this study, we demonstrated that AF and its derivatives are potent anthelminthic agents, particularly against Echinococcus multilocularis, which is the causative agent of alveolar echinococcosis. We measured the inhibitory activities of AF and its derivatives on the mitochondrial aerobic and anaerobic respiratory systems of E. multilocularis larvae. Several derivatives inhibited complex II (succinate:quinone reductase [SQR]; IC50 = 0.037 to 0.135 mM) and also complex I to III (NADH:cytochrome c reductase; IC50 = 0.008 to 0.401 mM), but not complex I (NADH:quinone reductase), indicating that mitochondrial complexes II and III are the targets. In particular, complex II inhibition in the anaerobic pathway was notable because E. multilocularis employs NADH:fumarate reductase (fumarate respiration), in addition to NADH oxidase (oxygen respiration), resulting in complete shutdown of ATP synthesis by oxidative phosphorylation. A structure-activity relationship study of E. multilocularis complex II revealed that the functional groups of AF are essential for inhibition. Binding mode prediction of AF derivatives to complex II indicated potential hydrophobic and hydrogen bond interactions between AF derivatives and amino acid residues within the quinone binding site. Ex vivo culture assays revealed that AF derivatives progressively reduced the viability of protoscoleces under both aerobic and anaerobic conditions. These findings confirm that AF and its derivatives are the first dual inhibitors of fumarate and oxygen respiration in E. multilocularis and are potential lead compounds in the development of anti-echinococcal drugs.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Antimicrobial Agents and Chemotherapy, art. no. e01428-22; 2023　","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Microbiology"}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1128/aac.01428-22","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2023 Enkai et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license."}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0066-4804","subitem_source_identifier_type":"ISSN"}]},"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":"Enkai, Shigehiro"}],"nameIdentifiers":[{"nameIdentifier":"124585","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kouguchi, Hirokazu"}],"nameIdentifiers":[{"nameIdentifier":"124586","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Inaoka, Daniel Ken"}],"nameIdentifiers":[{"nameIdentifier":"124587","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shiba, Tomoo"}],"nameIdentifiers":[{"nameIdentifier":"124588","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hidaka, Masahito"}],"nameIdentifiers":[{"nameIdentifier":"124589","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsuyama, Hiroyuki"}],"nameIdentifiers":[{"nameIdentifier":"124590","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sakura, Takaya"}],"nameIdentifiers":[{"nameIdentifier":"124591","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yagi, Kinpei"}],"nameIdentifiers":[{"nameIdentifier":"124592","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kita, Kiyoshi"}],"nameIdentifiers":[{"nameIdentifier":"124593","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-02-24"}],"displaytype":"detail","filename":"AAC67_e01428-22.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"AAC67_e01428-22.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/27934/files/AAC67_e01428-22.pdf"},"version_id":"05ff6784-bd20-4813-9ef0-c4fe2e6e2e98"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Echinococcus multilocularis","subitem_subject_scheme":"Other"},{"subitem_subject":"ascofuranone","subitem_subject_scheme":"Other"},{"subitem_subject":"structure-activity relationship","subitem_subject_scheme":"Other"},{"subitem_subject":"mitochondrial complex II","subitem_subject_scheme":"Other"},{"subitem_subject":"fumarate respiration","subitem_subject_scheme":"Other"},{"subitem_subject":"drug development","subitem_subject_scheme":"Other"},{"subitem_subject":"dual inhibitors","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":"Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis"}]},"item_type_id":"2","owner":"6","path":["36"],"pubdate":{"attribute_name":"公開日","attribute_value":"2023-02-24"},"publish_date":"2023-02-24","publish_status":"0","recid":"27934","relation_version_is_last":true,"title":["Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis"],"weko_creator_id":"6","weko_shared_id":-1},"updated":"2023-05-15T18:12:55.694331+00:00"}