Development of UTX-121 and its derivatives as novel matrix metalloproteinase-2/9 inhibitors using celecoxib as a lead compound

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Development of UTX-121 and its derivatives as novel matrix metalloproteinase-2/9 inhibitors using celecoxib as a lead compound

Persistent ID (NDL): info:ndljp/pid/12263336

Material type: 博士論文

Author: 山花, 啓梨

Publisher: -

Publication date: 2022-03-01

Material Format: Digital

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Name of awarding university/degree: 徳島大学,博士（工学）

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Note (General)：: Matrix metalloproteinases (MMP)-2/9 are closely associated with cancer malignancy, and it has been considered that the inhibition of these MMPs may be...

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Material Type: 博士論文
Title: Development of UTX-121 and its derivatives as novel matrix metalloproteinase-2/9 inhibitors using celecoxib as a lead compound
Author/Editor: 山花, 啓梨
Author Heading: 山花, 啓梨
Publication Date: 2022-03-01
Publication Date (W3CDTF): 2022-03-01
Alternative Title: Celecoxibをリードとした新規MMP-2/9阻害剤UTX-121およびその誘導体の開発
Degree grantor/type: 徳島大学
Date Granted: 2022-03-01
Date Granted (W3CDTF): 2022-03-01
Dissertation Number: 甲第3576号
Degree Type: 博士（工学）
Conferring No. (Dissertation): 甲第3576号
Text Language Code: eng
Subject Heading: matrix metalloproteinase-2/9
celecoxib
antitumor
antimetastasis
Target Audience: 一般
Note (General): Matrix metalloproteinases (MMP)-2/9 are closely associated with cancer malignancy, and it has been considered that the inhibition of these MMPs may be beneficial for enhancing the antitumor and antimetastatic activities of agents. In addition, celecoxib, a COX-2 selective inhibitor, has been reported to have a poor MMPs inhibitory activity, suggesting that it is a very promising drug as an anticancer and antimetastatic agent. We have revealed that UTX-121, which was converted the sulfonamide moiety of celecoxib into a methyl ester, significantly suppressed MT1-MMP-mediated MMP-2 activation and MMP-9 production. Furthermore, UTX-121 also inhibited the migration and invasion of cancer cells. We then searched for compounds with higher MMPs inhibitory activity using a structure-activity relationship (SAR) method based on UTX-121 as a lead compound. Among them, compounds 9c and 10c, in which the methyl moiety of the p-tolyl group in UTX-121 was substituted with F and Cl, showed higher antitumor and MMPs inhibitory activities than UTX-121. These findings suggest that compounds 9c and 10c could be potential lead compounds for the development of potent MMPs inhibitors.
Persistent ID (NDL): info:ndljp/pid/12263336
https://dl.ndl.go.jp/pid/12263336
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
https://dl.ndl.go.jp/collections/A00014
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2022-05-09T11:57:37+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
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Availability of remote photoduplication service: 可
Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/116963
Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション
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