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

“ An Efficient One Pot Multicomponent Synthesis of Dihydro Pyrazolyl Bithiazole Derivatives as Potential Anticancer Agents and Their Molecular Docking Studies”

Abstract A novel series of dihydropyrazolyl bithiazoles were efficiently synthesized through simple reaction conditions via one pot multicomponent reaction of 2-bromo-1-(4-methyl-2-phenyl thiazol-5-yl)ethan-1-one (1), thiosemicarbazide (2) and chalcones (3 a-k) in the presence of sodium hydroxide in ethanol under reflux condition. The reaction generates two potential five membered heterocylic pharmacophores i.e. Hantzsch thiazole and dihydropyrazole in one step through operational simplicity, shorter reaction time with high yields. The newly synthesized compounds were well characterized by IR, 1H, 13C NMR and Mass spectral data. All the newly synthesized compounds were evaluated for their anticancer activity against human cancer cell lines and calculated their binding energy values with respect to 3ert protein. The compounds 4f, 4g, 4h and 4j exhibited excellent activity against MCF-7 cancer cell line with IC50 Values of 3.47 ± 0.28, 1.36 ± 0.74, 3.76 ± 0.35 and 4.14 ± 0.26 µM concentrations and studied molecular interaction of probable target protein human Estrogen Receptor Alpha protein (3ert.pdb) using docking simulation.</jats:p

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