Tetrahydro-1,8-naphthyridinol analogues of alpha-tocopherol as antioxidants in lipid membranes and low-density lipoproteins
DC Field | Value | Language |
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dc.contributor.author | Nam, Tae-gyu | - |
dc.contributor.author | Rector, Christopher L. | - |
dc.contributor.author | Kim, Hye-young | - |
dc.contributor.author | Sonnen, Andreas F. -P. | - |
dc.contributor.author | Meyer, Roland | - |
dc.contributor.author | Nau, Werner M. | - |
dc.contributor.author | Atkinson, Jeffrey | - |
dc.contributor.author | Rintoul, Julia | - |
dc.contributor.author | Pratt, Derek A. | - |
dc.contributor.author | Porter, Ned A. | - |
dc.date.accessioned | 2021-06-23T19:06:52Z | - |
dc.date.available | 2021-06-23T19:06:52Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2007-08 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/43485 | - |
dc.description.abstract | Recently we demonstrated that the C(7)-unsubstituted tetrahydro-1,8-naphthyridin-3-ol has more than an order of magnitude better peroxyl radical trapping activity than alpha-tocopherol (alpha-TOH) in inhibited autoxidations in benzene. In order to prepare analogues more structurally related to alpha-TOH for further studies in vitro and in vivo, we developed synthetic approaches to C(7)-monoalkyl and C(7)-dialkyl analogues using a sequence involving (1) AgNO3-mediated hydroxymethyl radical addition to 1,8-naphthyridine, (2) regioselective alkyllithium addition by cyclic chelation in a nonpolar solvent, (3) iodination of the naphthyridine at C(3), and (4) CuI-medidated benzyloxylation of the aryl iodide followed by catalytic hydrogenolysis. An alpha-TOH isostere was prepared by a Wittig coupling of a C-16 side chain identical to that of alpha-TOH to the naphthyridinols. The C(7)-mono- and dialkyl analogues exhibited more than an order of magnitude higher antioxidant activity (k(inh) = (5.3-6.1) x 10(7) M-1 s(-1)) than alpha-TOH (k(inh) = 0.35 x 10(7) M-1 s(-1)) in benzene, as determined by a newly developed peroxyl radical clock. In addition to the strong antioxidant activity in benzene, the closest alpha-TOH analogue (naphthyridinol-based tocopherol, N-TOH) showed excellent inhibition of the oxidation of cholesteryl esters in human low-density lipoprotein and spared endogenous alpha-TOH in these experiments. Lateral diffusion of N-TOH in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes was comparable to that of alpha-TOH, suggesting that it will have good antioxidant characteristics in both membranes and lipoproteins. Furthermore, a binding assay using a fluorescent tocopherol analogue showed that N-TOH binds to recombinant human tocopherol transfer protein better than alpha-TOH itself, suggesting that distribution of unnatural antioxidants such as N-TOH in vivo is possible. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Tetrahydro-1,8-naphthyridinol analogues of alpha-tocopherol as antioxidants in lipid membranes and low-density lipoproteins | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Nam, Tae-gyu | - |
dc.identifier.doi | 10.1021/ja072371m | - |
dc.identifier.scopusid | 2-s2.0-34548169304 | - |
dc.identifier.wosid | 000248896400047 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.129, no.33, pp.10211 - 10219 | - |
dc.relation.isPartOf | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | - |
dc.citation.title | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | - |
dc.citation.volume | 129 | - |
dc.citation.number | 33 | - |
dc.citation.startPage | 10211 | - |
dc.citation.endPage | 10219 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | VITAMIN-E | - |
dc.subject.keywordPlus | BIOLOGICAL MOLECULES | - |
dc.subject.keywordPlus | FLUORESCENT-PROBE | - |
dc.subject.keywordPlus | CHAIN | - |
dc.subject.keywordPlus | AUTOXIDATION | - |
dc.subject.keywordPlus | DIFFUSION | - |
dc.subject.keywordPlus | OXIDATION | - |
dc.subject.keywordPlus | ALKYLLITHIUMS | - |
dc.subject.keywordPlus | PEROXIDATION | - |
dc.subject.keywordPlus | SPECIFICITY | - |
dc.subject.keywordAuthor | CHAIN-BREAKING ANTIOXIDANTS | - |
dc.subject.keywordAuthor | VITAMIN-E | - |
dc.subject.keywordAuthor | BIOLOGICAL MOLECULES | - |
dc.subject.keywordAuthor | FLUORESCENT-PROBE | - |
dc.subject.keywordAuthor | AUTOXIDATION | - |
dc.subject.keywordAuthor | PEROXIDATION | - |
dc.subject.keywordAuthor | DIFFUSION | - |
dc.subject.keywordAuthor | OXIDATION | - |
dc.subject.keywordAuthor | PHENOLS | - |
dc.subject.keywordAuthor | PROTEIN | - |
dc.identifier.url | https://pubs.acs.org/doi/10.1021/ja072371m | - |
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