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dc.contributor.author남태규-
dc.date.accessioned2019-06-24T05:13:44Z-
dc.date.available2019-06-24T05:13:44Z-
dc.date.issued2007-08-
dc.identifier.citationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v. 129, No. 33, Page. 10211-10219en_US
dc.identifier.issn0002-7863-
dc.identifier.urihttps://pubs.acs.org/doi/abs/10.1021/ja072371m-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/106811-
dc.description.abstractRecently 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.en_US
dc.language.isoen_USen_US
dc.publisherAMER CHEMICAL SOCen_US
dc.subjectCHAIN-BREAKING ANTIOXIDANTSen_US
dc.subjectVITAMIN-Een_US
dc.subjectBIOLOGICAL MOLECULESen_US
dc.subjectFLUORESCENT-PROBEen_US
dc.subjectAUTOXIDATIONen_US
dc.subjectPEROXIDATIONen_US
dc.subjectDIFFUSIONen_US
dc.subjectOXIDATIONen_US
dc.subjectPHENOLSen_US
dc.subjectPROTEINen_US
dc.titleTetrahydro-1,8-naphthyridinol analogues of alpha-tocopherol as antioxidants in lipid membranes and low-density lipoproteinsen_US
dc.typeArticleen_US
dc.relation.no33-
dc.relation.volume129-
dc.identifier.doi10.1021/ja072371m-
dc.relation.page10211-10219-
dc.relation.journalJOURNAL OF THE AMERICAN CHEMICAL SOCIETY-
dc.contributor.googleauthorNam, Tae-gyu-
dc.contributor.googleauthorRector, Christopher L.-
dc.contributor.googleauthorKim, Hye-young-
dc.contributor.googleauthorSonnen, Andreas F. -P.-
dc.contributor.googleauthorMeyer, Roland-
dc.contributor.googleauthorNau, Werner M.-
dc.contributor.googleauthorAtkinson, Jeffrey-
dc.contributor.googleauthorRintoul, Julia-
dc.contributor.googleauthorPratt, Derek A.-
dc.contributor.googleauthorPorter, Ned A.-
dc.relation.code2007205895-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF PHARMACY[E]-
dc.sector.departmentDEPARTMENT OF PHARMACY-
dc.identifier.pidtnam-
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COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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