| Title: | Synthesis of Resolvin E1 and Its Conformationally Restricted Cyclopropane Congeners with Potent Anti-Inflammatory Effect |
| Authors: | Ishimura, Kohei Browse this author |
| Fukuda, Hayato Browse this author |
| Fujiwara, Koichi Browse this author →KAKEN DB |
| Muromoto, Ryuta Browse this author →KAKEN DB |
| Hirashima, Koki Browse this author |
| Murakami, Yuto Browse this author |
| Watanabe, Mizuki Browse this author →KAKEN DB |
| Ishihara, Jun Browse this author |
| Matsuda, Tadashi Browse this author →KAKEN DB |
| Shuto, Satoshi Browse this author →KAKEN DB |
| Keywords: | Resolvin E1 |
| anti-inflammatory |
| cyclopropane congener |
| proresolving lipid mediator |
| Issue Date: | 21-Jan-2021 |
| Publisher: | American Chemical Society |
| Journal Title: | ACS medicinal chemistry letters |
| Volume: | 12 |
| Issue: | 2 |
| Start Page: | 256 |
| End Page: | 261 |
| Publisher DOI: | 10.1021/acsmedchemlett.0c00639 |
| Abstract: | RvE1 (1) is an endogenous lipid mediator with very potent anti-inflammatory activity, which is due to the inhibition of neutrophil chemotaxis and inflammatory cytokine production and the promotion of macrophage phagocytosis. On the basis of the conformational analysis of RvE1, we designed its four cyclopropane congeners (2a-d), in which the conformationally flexible terminal C1-C4 moiety of RvE1 was rigidified by introducing stereoisomeric cyclopropanes. The four congeners and also RvE1 were efficiently synthesized via a common synthetic route. The evaluation of the anti-inflammatory effects of the compounds in mice resulted in the identification of trans-beta-CP-RvE1 (2d), which was significantly more active than RvE1, as a potential lead for antiinflammatory drugs of a novel mechanism of action. |
| Rights: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS medicinal chemistry letters, copyright c American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00639. |
| https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00639 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/83926 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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