WEKO3
アイテム
{"_buckets": {"deposit": "0e56e437-169e-471a-a2fa-19ab28b589ad"}, "_deposit": {"created_by": 12, "id": "2000117", "owner": "12", "owners": [12], "pid": {"revision_id": 0, "type": "depid", "value": "2000117"}, "status": "published"}, "_oai": {"id": "oai:obihiro.repo.nii.ac.jp:02000117", "sets": ["5"]}, "author_link": ["357"], "control_number": "2000117", "item_2_biblio_info_7": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2023-12-07", "bibliographicIssueDateType": "Issued"}, "bibliographicPageStart": "106668", "bibliographicVolumeNumber": "192", "bibliographic_titles": [{"bibliographic_title": "European Journal of Pharmaceutical Sciences", "bibliographic_titleLang": "en"}]}]}, "item_2_description_19": {"attribute_name": "フォーマット", "attribute_value_mlt": [{"subitem_description": "application/pdf", "subitem_description_language": "en", "subitem_description_type": "Other"}]}, "item_2_description_5": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "African trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock\u0027s most virulent trypanosome species. There is currently no vaccine against trypanosomiasis; its treatment relies solely on chemotherapy. However, pathogenic resistance has been established against trypanocidal agents in clinical use. This underscores the need to develop new therapeutics to curb trypanosomiasis. Many nitroheterocyclic drugs or compounds, including nitrofurantoin, possess antiparasitic activities in addition to their clinical use as antibiotics. The current study evaluated the in vitro trypanocidal potency and in vivo treatment efficacy of previously synthesized antileishmanial active oligomeric ethylene glycol derivatives of nitrofurantoin. The trypanocidal potency of analogues 2a-o varied among the trypanosome species; however, T. congolense strain IL3000 was more susceptible to these drug candidates than the other human and animal trypanosomes. The arylated analogues 2k (IC50 0.04 µM; SI \u003e6365) and 2l (IC50 0.06 µM; SI 4133) featuring 4-chlorophenoxy and 4-nitrophenoxy moieties, respectively, were revealed as the most promising antitrypanosomal agents of all analogues against T. congolense strain IL3000 trypomastigotes with nanomolar activities. In a preliminary in vivo study involving T. congolense strain IL3000 infected BALB/c mice, the oral administration of 100 mg/kg/day of 2k caused prolonged survival up to 18 days post-infection relative to the infected but untreated control mice which survived 9 days post-infection. However, no cure was achieved due to its poor solubility in the in vivo testing medium, assumably leading to low oral bioavailability. These results confirm the importance of the physicochemical properties lipophilicity and water solubility in attaining not only in vitro trypanocidal potency but also in vivo treatment efficacy. Future work will focus on the chemical optimization of 2k through the investigation of analogues containing solubilizing groups at certain positions on the core structure to improve solubility in the in vivo testing medium which, in the current investigation, is the biggest stumbling block in successfully treating either animal or human Trypanosoma infections. © 2023", "subitem_description_language": "en", "subitem_description_type": "Abstract"}]}, "item_2_publisher_8": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "Elsevier", "subitem_publisher_language": "en"}]}, "item_2_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.ejps.2023.106668", "subitem_relation_type_select": "DOI"}}]}, "item_2_rights_15": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2023 The Authors.", "subitem_rights_language": "en"}]}, "item_2_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "09280987", "subitem_source_identifier_type": "PISSN"}]}, "item_2_subject_21": {"attribute_name": "日本十進分類法", "attribute_value_mlt": [{"subitem_subject": "649", "subitem_subject_language": "en", "subitem_subject_scheme": "NDC"}]}, "item_2_text_25": {"attribute_name": "文献提供者", "attribute_value_mlt": [{"subitem_text_value": "菅沼啓輔"}]}, "item_2_textarea_24": {"attribute_name": "作業記録", "attribute_value_mlt": [{"subitem_textarea_language": "en", "subitem_textarea_value": "Scopus202312-04, 2023/12/20菅沼先生にメール送信, 2024/1/23 「これまで&これからの論文すべてOK」と回答有、2024/1/24登録作業"}]}, "item_2_version_type_20": {"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": "Janse van Rensburg, Helena D.", "creatorNameLang": "en"}]}, {"creatorNames": [{"creatorName": "N\u0027Da, David D.", "creatorNameLang": "en"}]}, {"creatorNames": [{"creatorName": "Suganuma, Keisuke", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "357", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "9000345306716", "nameIdentifierScheme": "CiNii ID", "nameIdentifierURI": "http://ci.nii.ac.jp/nrid/9000345306716"}, {"nameIdentifier": "60772184", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=60772184"}, {"nameIdentifier": "11922960", "nameIdentifierScheme": "researchmap", "nameIdentifierURI": "https://researchmap.jp/11922960"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_access", "date": [{"dateType": "Available", "dateValue": "2024-01-24"}], "download_preview_message": "", "file_order": 0, "filename": "suganuma_1-s2.0-S0928098723002968-main-1.pdf", "filesize": [{"value": "2 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_5", "mimetype": "application/pdf", "size": 2000000.0, "url": {"label": "fulltext", "url": "https://obihiro.repo.nii.ac.jp/record/2000117/files/suganuma_1-s2.0-S0928098723002968-main-1.pdf"}, "version_id": "9525b50b-1b6f-4ff3-b126-879159cc4793"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "African trypanosome", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Ethylene glycol", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Nitrofurantoin", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Nitroheterocycle", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Trypanocidal potency", "subitem_subject_language": "en", "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": "In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives", "subitem_title_language": "en"}]}, "item_type_id": "2", "owner": "12", "path": ["5"], "permalink_uri": "https://obihiro.repo.nii.ac.jp/records/2000117", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2024-01-24"}, "publish_date": "2024-01-24", "publish_status": "0", "recid": "2000117", "relation": {}, "relation_version_is_last": true, "title": ["In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives"], "weko_shared_id": -1}
In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives
https://obihiro.repo.nii.ac.jp/records/2000117
https://obihiro.repo.nii.ac.jp/records/20001178d211777-fc1a-4ddb-a83e-f2cd3bdc5fb4
名前 / ファイル | ライセンス | アクション |
---|---|---|
fulltext (2 MB)
|
Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
公開日 | 2024-01-24 | |||||||||||
タイトル | ||||||||||||
言語 | en | |||||||||||
タイトル | In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | African trypanosome | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Ethylene glycol | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Nitrofurantoin | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Nitroheterocycle | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Trypanocidal potency | |||||||||||
資源タイプ | ||||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||
資源タイプ | journal article | |||||||||||
著者 |
Janse van Rensburg, Helena D.
× Janse van Rensburg, Helena D.
× N'Da, David D.
× Suganuma, Keisuke
WEKO
357
|
|||||||||||
抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | African trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock's most virulent trypanosome species. There is currently no vaccine against trypanosomiasis; its treatment relies solely on chemotherapy. However, pathogenic resistance has been established against trypanocidal agents in clinical use. This underscores the need to develop new therapeutics to curb trypanosomiasis. Many nitroheterocyclic drugs or compounds, including nitrofurantoin, possess antiparasitic activities in addition to their clinical use as antibiotics. The current study evaluated the in vitro trypanocidal potency and in vivo treatment efficacy of previously synthesized antileishmanial active oligomeric ethylene glycol derivatives of nitrofurantoin. The trypanocidal potency of analogues 2a-o varied among the trypanosome species; however, T. congolense strain IL3000 was more susceptible to these drug candidates than the other human and animal trypanosomes. The arylated analogues 2k (IC50 0.04 µM; SI >6365) and 2l (IC50 0.06 µM; SI 4133) featuring 4-chlorophenoxy and 4-nitrophenoxy moieties, respectively, were revealed as the most promising antitrypanosomal agents of all analogues against T. congolense strain IL3000 trypomastigotes with nanomolar activities. In a preliminary in vivo study involving T. congolense strain IL3000 infected BALB/c mice, the oral administration of 100 mg/kg/day of 2k caused prolonged survival up to 18 days post-infection relative to the infected but untreated control mice which survived 9 days post-infection. However, no cure was achieved due to its poor solubility in the in vivo testing medium, assumably leading to low oral bioavailability. These results confirm the importance of the physicochemical properties lipophilicity and water solubility in attaining not only in vitro trypanocidal potency but also in vivo treatment efficacy. Future work will focus on the chemical optimization of 2k through the investigation of analogues containing solubilizing groups at certain positions on the core structure to improve solubility in the in vivo testing medium which, in the current investigation, is the biggest stumbling block in successfully treating either animal or human Trypanosoma infections. © 2023 | |||||||||||
言語 | en | |||||||||||
書誌情報 |
en : European Journal of Pharmaceutical Sciences 巻 192, p. 106668, 発行日 2023-12-07 |
|||||||||||
出版者 | ||||||||||||
言語 | en | |||||||||||
出版者 | Elsevier | |||||||||||
ISSN | ||||||||||||
収録物識別子タイプ | PISSN | |||||||||||
収録物識別子 | 09280987 | |||||||||||
DOI | ||||||||||||
関連タイプ | isIdenticalTo | |||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | https://doi.org/10.1016/j.ejps.2023.106668 | |||||||||||
権利 | ||||||||||||
言語 | en | |||||||||||
権利情報 | © 2023 The Authors. | |||||||||||
フォーマット | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
言語 | en | |||||||||||
著者版フラグ | ||||||||||||
出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
日本十進分類法 | ||||||||||||
言語 | en | |||||||||||
主題Scheme | NDC | |||||||||||
主題 | 649 |