Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 남태규 | - |
dc.date.accessioned | 2018-04-26T08:15:28Z | - |
dc.date.available | 2018-04-26T08:15:28Z | - |
dc.date.issued | 2016-10 | - |
dc.identifier.citation | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v. 26, No. 19, Page. 4587-4591 | en_US |
dc.identifier.issn | 0960-894X | - |
dc.identifier.issn | 1464-3405 | - |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0960894X16309076?via%3Dihub | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/70860 | - |
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. | en_US |
dc.description.sponsorship | This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI15C0542). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | en_US |
dc.subject | 6-Amino-2,4,5-trimethylpyridin-3-ol | en_US |
dc.subject | Cell adhesion | en_US |
dc.subject | Inflammatory bowel disease | en_US |
dc.subject | TNBS-induced colitis | en_US |
dc.subject | TNF-α | en_US |
dc.title | In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease | en_US |
dc.type | Article | en_US |
dc.relation.no | 19 | - |
dc.relation.volume | 26 | - |
dc.identifier.doi | 10.1016/j.bmcl.2016.08.075 | - |
dc.relation.page | 4587-4591 | - |
dc.relation.journal | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | - |
dc.contributor.googleauthor | Banskota, S | - |
dc.contributor.googleauthor | Kang, HE | - |
dc.contributor.googleauthor | Kim, DG | - |
dc.contributor.googleauthor | Park, SW | - |
dc.contributor.googleauthor | Jang, H | - |
dc.contributor.googleauthor | Karmacharya, U | - |
dc.contributor.googleauthor | Jeong, BS | - |
dc.contributor.googleauthor | Kim, JA | - |
dc.contributor.googleauthor | Nam, TG | - |
dc.relation.code | 2016000607 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | tnam | - |
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