Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis

Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD

Bis coumarinyl bis triazolothiadiazinyl ethane derivatives: Synthesis, antiviral activity evaluation, and molecular docking studies

© 2018 Taylor & Francis. A series of novel 3,3′-(3,3′-(dihydroxy/hydroxyethane-1,2-diyl)bis(7H-[1,2,4]triazolo[3,4-b]triazolo[3,4-b[1,3,4]thiadiazine-6,3-diyl))bis(2H-chromen-2-ones) were prepared by the condensation of thiocarbohydrazide with tartaric acid or malic acid followed by various 3-(2-bromoacetyl)-2H-chromen-2-ones in two steps with good yields. All the synthesized compounds were characterized by analytical and spectral (IR, 1H NMR, 13C NMR, and mass) data. These synthesized bis(triazolothiadiazinyl coumarin) compounds were evaluated for broad spectrum of antiviral activity. Among all the tested compounds, compound 5f exhibited antiviral activity against H1N1 virus. The molecular docking studies of these compounds against H1N1 neuraminidase enzyme were performed. The binding affinity and binding values were compared with standard drugs.status: publishe

Bis coumarinyl bis triazolothiadiazinyl ethane derivatives: Synthesis, antiviral activity evaluation, and molecular docking studies

<p>A series of novel 3,3′-(3,3′-(dihydroxy/hydroxyethane-1,2-diyl)bis(7<i>H</i>-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine-6,3-diyl))bis(2<i>H</i>-chromen-2-ones) were prepared by the condensation of thiocarbohydrazide with tartaric acid or malic acid followed by various 3-(2-bromoacetyl)-2<i>H</i>-chromen-2-ones in two steps with good yields. All the synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and mass) data. These synthesized bis(triazolothiadiazinyl coumarin) compounds were evaluated for broad spectrum of antiviral activity. Among all the tested compounds, compound <b>5f</b> exhibited antiviral activity against H1N1 virus. The molecular docking studies of these compounds against H1N1 neuraminidase enzyme were performed. The binding affinity and binding values were compared with standard drugs.</p