In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease
DC Field | Value | Language |
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dc.contributor.author | Banskota, Suhrid | - |
dc.contributor.author | Kang, Han-eol | - |
dc.contributor.author | Kim, Dong-Guk | - |
dc.contributor.author | Park, Sang Won | - |
dc.contributor.author | Jang, Hyeonjin | - |
dc.contributor.author | Karmacharya, Ujjwala | - |
dc.contributor.author | Jeong, Byeong-Seon | - |
dc.contributor.author | Kim, Jung-Ae | - |
dc.contributor.author | Nam, Tae-gyu | - |
dc.date.accessioned | 2021-06-22T16:03:10Z | - |
dc.date.available | 2021-06-22T16:03:10Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2016-10 | - |
dc.identifier.issn | 0960-894X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/12616 | - |
dc.description.abstract | Although the pathogenesis of inflammatory bowel disease (IBD) is complex, attachment and infiltration of leukocytes to gut epithelium induced by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) represents the initial step of inflammation in IBD. Previously, we have reported that some 6-amino-2,4,5-trimethylpyridin-3-ols have significant levels of antiangiogenic activity via PI3K inhibition. Based on the reports that angiogenesis is involved in the aggravation of IBD and that PI3K is a potential target for IBD therapy, we investigated whether the scaffold has inhibitory activity against in vitro and in vivo models of colitis. Many analogues showed >80% inhibition against TNF-alpha-induced monocyte adhesion to colon epithelial cells at 1 mu M. Compound 8m showed IC50 = 0.19 mu M, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA, IC50 = 18.1 mM), a positive control. In a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, orally administered 8m dramatically ameliorated TNBS-induced colon inflammation. It was demonstrated by a high level of suppression in myeloperoxidase (MPO), a surrogate marker of colitis, as well as almost perfect recovery of colon and body weights in a dose-dependent manner. Compared to sulfasalazine, a prodrug of 5-ASA, compound 8m showed >300-fold better efficacy in those parameters. Taken together, 6-amino-2,4,5-trimethylpyridin-3-ols can provide a novel platform for anti-IBD drug discovery. (C) 2016 Elsevier Ltd. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.title | In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Nam, Tae-gyu | - |
dc.identifier.doi | 10.1016/j.bmcl.2016.08.075 | - |
dc.identifier.scopusid | 2-s2.0-84985961153 | - |
dc.identifier.wosid | 000383359400007 | - |
dc.identifier.bibliographicCitation | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.26, no.19, pp.4587 - 4591 | - |
dc.relation.isPartOf | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | - |
dc.citation.title | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | - |
dc.citation.volume | 26 | - |
dc.citation.number | 19 | - |
dc.citation.startPage | 4587 | - |
dc.citation.endPage | 4591 | - |
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 | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.subject.keywordPlus | INTESTINAL INFLAMMATION | - |
dc.subject.keywordPlus | CROHNS-DISEASE | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | COLITIS | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | ASSAY | - |
dc.subject.keywordPlus | RAT | - |
dc.subject.keywordPlus | IBD | - |
dc.subject.keywordAuthor | Inflammatory bowel disease | - |
dc.subject.keywordAuthor | TNF-alpha | - |
dc.subject.keywordAuthor | 6-Amino-2,4,5-trimethylpyridin-3-ol | - |
dc.subject.keywordAuthor | Cell adhesion | - |
dc.subject.keywordAuthor | TNBS-induced colitis | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0960894X16309076?via%3Dihub | - |
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