Synthesis and evaluation of 6-heteroarylamino-2,4,5-trimethylpyridin-3-ols as inhibitors of TNF-alpha-induced cell adhesion and inflammatory bowel diseaseopen access
- Authors
- Park, Sang Won; Banskota, Suhrid; Gurung, Pallavi; Jin, You Jin; Kang, Han-eol; Chaudhary, Chhabi Lat; Lee, Sang Yeul; Jeong, Byeong-Seon; Kim, Jung-Ae; Nam, Tae-gyu
- Issue Date
- Aug-2018
- Publisher
- ROYAL SOC CHEMISTRY
- Keywords
- INTESTINAL INFLAMMATION; THERAPEUTIC TARGETS; CROHNS-DISEASE; IBD; PATHOGENESIS6-AMINO-2,4,5-TRIMETHYLPYRIDIN-3-OLS; IL-10; ASSAY; RAT
- Citation
- MEDCHEMCOMM, v.9, no.8, pp.1305 - 1310
- Indexed
- SCIE
SCOPUS
- Journal Title
- MEDCHEMCOMM
- Volume
- 9
- Number
- 8
- Start Page
- 1305
- End Page
- 1310
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/5710
- DOI
- 10.1039/c8md00156a
- ISSN
- 2040-2503
- Abstract
- Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract with complex pathogenesis. Here, we synthesized 6-heteroarylamino analogues to inhibit TNF-alpha-induced adhesion of monocytes to colon epithelial cells which are implicated in the initial inflammation process of IBD. The best analogue, 16a, showed IC50 = 0.29 mu M, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA), a positive control. Oral administration of 6f and 16a dramatically ameliorated 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colon inflammation in rat. The ameliorating effects were accompanied by a high level of recovery in colon and body weights and in the myeloperoxidase (MPO) level. Consistently, the compounds suppressed the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1). Moreover, they significantly suppressed the expression of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-6 while increasing the level of IL-10, an anti-inflammatory cytokine.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.