P030 Inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory cell adhesion and recruitment to colon epithelium
Jeong B.-S.*1, Banskota S.1, Kang H.-e.2, Kim J.-A.1, Nam T.-g.2
1Yeungnam University, College of Pharmacy, Gyeongsan, South Korea 2Hanyang University, College of Pharmacy, Ansan, South Korea
The pathogenesis of inflammatory bowel disease (IBD) is complex, and a useful therapeutic marker has not been proposed, yet. The role of PI3K/Akt pathway, however, is highlighted and suggested as a target for IBD therapy. Previously, we showed that 6-amino-2,4,5-trimethyl-pyridin-3-ols significantly inhibited angiogenesis induced by VEGF and serotonin. The structure-activity relationship and dose-dependency in antiangiogenic activity of the pyridinol derivatives clearly suggest that the compounds inhibit the common target molecule involved in both VEGF and serotonin signaling such as phosphoinositide-3-kinase (PI3K)/Akt. In the present study, we examined whether 6-amino-2,4,5-trimethyl-pyridin-3-ols suppress intestinal inflammation.
Based on the notion that IBD is of complex etiology, we tried a phenotype-based primary screening to inhibit the pathological action of TNF-α, instead of conducting a specific target-based approach to directly target TNF-α molecule. The anti-inflammatory activity
We synthesized 6-amino-2,4,5,-trimethylpyridin-3-ols and tested them in colitis models