Synthesis, activity and mechanism of alkoxy-, carbamato-, sulfonamido-, thioureido-, and ureido-derivatives of 2,4,5-trimethylpyridin-3-ol against inflammatory bowel disease

Autor: Chhabi Lal Chaudhary, Pallavi Gurung, Seoul Jang, Suhrid Banskota, Tae-Gyu Nam, Jung-Ae Kim, Byeong-Seon Jeong
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 1-20 (2020)
Druh dokumentu: article
ISSN: 1475-6366
1475-6374
14756366
DOI: 10.1080/14756366.2019.1677637
Popis: Inflammatory bowel disease (IBD) is a chronic immuno-inflammation in gastrointestinal tract. We have evaluated the activity of the compounds to inhibit the adhesion of monocytes to colon epithelial cells is triggered by a pro-inflammatory cytokine, tumour necrosis factor (TNF)-α. The in vitro activity of the compounds, 13b (an ureido-derivative), 14c, 14j, 14k, 14n (thioureido-), 18c and 18d (sulfonamido-), was in correlation with in vivo anti-colitis activity revealed as significant recovery in body- and colon-weights and colon myeloperoxidase level, a biochemical marker of inflammation reflecting neutrophil infiltration. In vivo, TNBS-induced changes in the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10, and TGF-β), NLRP3 inflammasome components (NLRP-3, Caspase-1, and IL-18), and epithelial junction molecules (E-cadherin, claudin2/3, and ZO-1) were blocked and recovered by oral administration of the compounds (1 mg/kg). Compound 14n which showed the best efficacy can be a promising lead for orally available therapeutics for pathology of IBD.
Databáze: Directory of Open Access Journals
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