Design and Synthesis of Benzene Congeners of Resolvin E2, a Proresolving Lipid Mediator, as Its Stable Equivalents
| Autor: | Tadashi Matsuda, Satoshi Shuto, Jun Ishihara, Koki Hirashima, Hayato Fukuda, Kohei Ishimura, Yuto Murakami, Ryuta Muromoto, Koichi Fujiwara, Mizuki Watanabe |
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| Rok vydání: | 2019 |
| Předmět: |
Diene
010405 organic chemistry Stereochemistry Organic Chemistry Lipid signaling 01 natural sciences Biochemistry 0104 chemical sciences Stille reaction 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Equivalent chemistry Mechanism of action Drug Discovery medicine Moiety medicine.symptom Benzene Resolvin |
| Zdroj: | ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| Popis: | [Image: see text] Resolvins (Rvs) are highly potent anti-inflammatory lipid mediators that are chemically and biologically unstable because of their polyunsaturated structures. To address this issue, we designed benzene congeners of RvE2, i.e., o-, m-, and p-BZ-RvE2s, as stable equivalents of RvE2 by replacing the unstable skipped diene moiety with a benzene ring on the basis of computational conformation studies and synthesized these congeners via a short common route through two Stille couplings. o-BZ-RvE2 exhibited more potent anti-inflammatory activity and much higher metabolic stability than RvE2. Thus, o-BZ-RvE2 was identified as a stable equivalent of RvE2, which is useful as a lead for anti-inflammatory drugs with a new mechanism of action as well as a biotool for investigating RvE2-mediated inflammation resolving pathways. |
| Databáze: | OpenAIRE |
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