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Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging.
https://repo.qst.go.jp/records/74737
https://repo.qst.go.jp/records/74737400f48bd-1f99-4381-a35b-49d6ec6e247b
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-03-15 | |||||
| タイトル | ||||||
| タイトル | Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 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 | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Effendi, Nurmaya
× Effendi, Nurmaya× Mishiro, Kenji× Takarada, Takeshi× Nishii, Ryuichi× Yamada, Daisuke× Shiba, Kazuhiro× Kinuya, Seigo× Odani, Akira× Ogawa, Kazuma× Nishii, Ryuichi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Several malignant tumors and fibrotic diseases are associated with PDGFRβ overexpression and excessive signaling, making this receptor attractive for molecular targeting and imaging approaches. A series of benzo[d]imidazole-quinoline derivatives were designed and synthesized to develop radioiodinated compounds as PDGFRβ-specific imaging probes. The structure activity relationship (SAR) evaluation of the designed compounds was performed. Among them, 2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (5a) and 4-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (5d) exhibited a relatively high PDGFRβ-TK inhibitory potency, whereas iodinated 5a derivative 5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (8) exhibited a superior inhibitory potency as PDGFRβ inhibitor than iodinated 5d derivative 4-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (11). Furthermore, [I]8 and [I]11 were synthesized and evaluated for PDGFRβ radioligand ability, both in vitro and in vivo. Cellular uptake experiments showed that [I]8 had a higher uptake in BxPC3-luc cells as PDGFRβ-positive cells than [I]11. Incubation of [I]8 after pretreatment of PDGFRβ ligands significantly reduced the uptake of [I]8. In biodistribution experiments using tumor-bearing mice, [I]8 accumulation in the tumor 1 h postinjection was higher than that of the benzo[d]imidazol-quinoline derivative [I]IIQP, used in our previous research. These results indicate that [I]8 could be a promising PDGFRβ imaging agent. Although its clinical application requires further structural modifications, the results obtained in this research may be useful for the development of PDGFRβ-specific radioligands. | |||||
| 書誌情報 |
Bioorganic & medicinal chemistry 巻 27, 号 2, p. 383-393, 発行日 2019-01 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0968-0896 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 30563725 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.bmc.2018.12.016 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S0968089618315414 | |||||
