Minimalistic Principles for Designing Small Molecules with Multiple Reactivities against Pathological Factors in Dementia

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dc.contributor.authorKim, Mingeunko
dc.contributor.authorKang, Juhyeko
dc.contributor.authorLee, Misunko
dc.contributor.authorHan, Jiyeonko
dc.contributor.authorNam, Geewooko
dc.contributor.authorTak, Eunyoungko
dc.contributor.authorMin Sun Kimko
dc.contributor.authorLee, Hyuck Jinko
dc.contributor.authorNam, Eunjuko
dc.contributor.authorPark, Jiyongko
dc.contributor.authorOh, Soo Jinko
dc.contributor.authorLee, Ji-Yoonko
dc.contributor.authorLee, Joo-Yongko
dc.contributor.authorBaik, Mu-Hyunko
dc.contributor.authorLim, Mi Heeko
dc.date.accessioned2020-06-17T05:20:09Z-
dc.date.available2020-06-17T05:20:09Z-
dc.date.created2020-05-11-
dc.date.issued2020-05-
dc.identifier.citationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.142, no.18, pp.8183 - 8193-
dc.identifier.issn0002-7863-
dc.identifier.urihttp://hdl.handle.net/10203/274704-
dc.description.abstractMultiple pathogenic elements, including reactive oxygen species, amyloidogenic proteins, and metal ions, are associated with the development of neurodegenerative disorders. We report minimalistic redox-based principles for preparing compact aromatic compounds by derivatizing the phenylene moiety with various functional groups. These molecular agents display enhanced reactivities against multiple targets such as free radicals, metal-free amyloid-beta (A beta), and metal-bound A beta that are implicated in the most common form of dementia, Alzheimer's disease (AD). Mechanistic studies reveal that the redox properties of these reagents are essential for their function. Specifically, they engage in oxidative reactions with metal-free and metal-bound A beta, leading to chemical modifications of the A beta peptides to form covalent adducts that alter the aggregation of A beta. Moreover, the administration of the most promising candidate significantly attenuates the amyloid pathology in the brains of AD transgenic mice and improves their cognitive defects. Our studies demonstrate an efficient and effective redox-based strategy for incorporating multiple functions into simple molecular reagents.-
dc.languageEnglish-
dc.publisherAMER CHEMICAL SOC-
dc.titleMinimalistic Principles for Designing Small Molecules with Multiple Reactivities against Pathological Factors in Dementia-
dc.typeArticle-
dc.identifier.wosid000535173500019-
dc.identifier.scopusid2-s2.0-85084746189-
dc.type.rimsART-
dc.citation.volume142-
dc.citation.issue18-
dc.citation.beginningpage8183-
dc.citation.endingpage8193-
dc.citation.publicationnameJOURNAL OF THE AMERICAN CHEMICAL SOCIETY-
dc.identifier.doi10.1021/jacs.9b13100-
dc.contributor.localauthorBaik, Mu-Hyun-
dc.contributor.localauthorLim, Mi Hee-
dc.contributor.nonIdAuthorKang, Juhye-
dc.contributor.nonIdAuthorLee, Misun-
dc.contributor.nonIdAuthorNam, Geewoo-
dc.contributor.nonIdAuthorTak, Eunyoung-
dc.contributor.nonIdAuthorMin Sun Kim-
dc.contributor.nonIdAuthorLee, Hyuck Jin-
dc.contributor.nonIdAuthorPark, Jiyong-
dc.contributor.nonIdAuthorOh, Soo Jin-
dc.contributor.nonIdAuthorLee, Ji-Yoon-
dc.contributor.nonIdAuthorLee, Joo-Yong-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusAROMATIC FREE-RADICALS-
dc.subject.keywordPlusAMYLOID-BETA PEPTIDE-
dc.subject.keywordPlusALZHEIMERS-DISEASE-
dc.subject.keywordPlusOXIDATIVE STRESS-
dc.subject.keywordPlusANTIOXIDANT CAPACITY-
dc.subject.keywordPlusP-PHENYLENEDIAMINE-
dc.subject.keywordPlusAGGREGATION-
dc.subject.keywordPlusCHEMISTRY-
dc.subject.keywordPlusBIOLOGY-
dc.subject.keywordPlusTARGET-
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