Indole-Substituted Benzothiazoles and Benzoxazoles as Selective and Reversible MAO-B Inhibitors for Treatment of Parkinson's Disease
DC Field | Value | Language |
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dc.contributor.author | Nam, Min-Ho | - |
dc.contributor.author | Park, Moosung | - |
dc.contributor.author | Park, Hyeri | - |
dc.contributor.author | Kim, Youngjae | - |
dc.contributor.author | Yoon, Seulki | - |
dc.contributor.author | Sawant, Vikram Shahaji | - |
dc.contributor.author | Cho, Ji Won | - |
dc.contributor.author | Park, Jong-Hyun | - |
dc.contributor.author | Park, Ki Duk | - |
dc.contributor.author | Min, Sun-Joon | - |
dc.contributor.author | Lee, C. Justin | - |
dc.contributor.author | Chooaii, Hyunah | - |
dc.date.accessioned | 2021-06-22T14:01:47Z | - |
dc.date.available | 2021-06-22T14:01:47Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2017-07 | - |
dc.identifier.issn | 1948-7193 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/9480 | - |
dc.description.abstract | To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-IN-indol-5-yl)benzo[d]-thiazole with an IC50 value of 28 nM with no apparent effect on MAO-A activity at 10 mu M. Based on the reversibility assay, compound 5b turned out to be fully reversible with over 95% of recovery of enzyme activity after washout of the compound. Compound Sb showed a reasonable stability in human liver microsomes and did not affect the activities of CYP isozymes, suggesting an absence of high-risk drug-drug interaction. In an in vivo MPTP-induced animal model of Parkinson's disease, oral administration of compound 5b showed neuroprotection of nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevention of MPTP-induced parkinsonism as revealed by motor behavioral assay of vertical grid test. In summary, the novel, reversible, and selective MAO-B inhibitor compound 5b was synthesized and characterized. We propose compound 5b as an effective therapeutic compound for relieving parkinsonism. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | American Chemical Society | - |
dc.title | Indole-Substituted Benzothiazoles and Benzoxazoles as Selective and Reversible MAO-B Inhibitors for Treatment of Parkinson's Disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Min, Sun-Joon | - |
dc.identifier.doi | 10.1021/acschemneuro.7b00050 | - |
dc.identifier.scopusid | 2-s2.0-85024833338 | - |
dc.identifier.wosid | 000406174500013 | - |
dc.identifier.bibliographicCitation | ACS Chemical Neuroscience, v.8, no.7, pp.1519 - 1529 | - |
dc.relation.isPartOf | ACS Chemical Neuroscience | - |
dc.citation.title | ACS Chemical Neuroscience | - |
dc.citation.volume | 8 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1519 | - |
dc.citation.endPage | 1529 | - |
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 | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.subject.keywordPlus | MONOAMINE-OXIDASE-B | - |
dc.subject.keywordPlus | L-DOPA | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | DRUG | - |
dc.subject.keywordPlus | SAFINAMIDE | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | METAANALYSIS | - |
dc.subject.keywordPlus | DERIVATIVES | - |
dc.subject.keywordPlus | RASAGILINE | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordAuthor | MAO-B | - |
dc.subject.keywordAuthor | MAO-B inhibitor | - |
dc.subject.keywordAuthor | Parkinson&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | benzothiazole | - |
dc.subject.keywordAuthor | benzoxazole | - |
dc.subject.keywordAuthor | MPTP-induced animal model | - |
dc.identifier.url | https://pubs.acs.org/doi/10.1021/acschemneuro.7b00050 | - |
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