Resultative Compound Verb in Modern Chinese : A Comment on Imai(1985) and Lu(1986)

<p>A. API and DMO suppresses NF-κB DNA binding ability in HCT116 cells. HCT116 cells were treated with DMO and API at indicated doses, nuclear extracts were prepared, and 20 μg of the nuclear extract protein was used for the ELISA-based DNA-binding assay *p<0.05; **p<0.005). B & C. NF-κB responsive elements linked to a luciferase reporter gene were transfected with wild-type or dominant-negative IκB and transfected cancer cells were treated at indicated doses for 6 h and luciferase activity was measured as described in Materials and Methods section. All luciferase experiments were done in triplicate and repeated twice (*p<0.05; **p<0.005). D. API abrogates constitutive IκBα phosphorylation in dose-dependent manner in HCT116 cells. HCT116 cells were treated with different concentrations of API (0, 5, 10 and 20 μM) for 6 h and cytoplasmic extract was prepared. Lysates were resolved on SDS gel and electrotransferred to a nitrocellulose membrane and probed with anti-phospho-IκBα/IκBα. The blot was washed, exposed to HRP-conjugated secondary antibodies for 1 h, and finally examined by chemiluminescence. GAPDH was used as loading control.</p

A One Pot Synthesis of Novel Bioactive Tri-Substitute-Condensed-Imidazopyridines that Targets Snake Venom Phospholipase A₂

<div><p>Drugs such as necopidem, saripidem, alpidem, zolpidem, and olprinone contain nitrogen-containing bicyclic, condensed-imidazo[1,2-α]pyridines as bioactive scaffolds. In this work, we report a high-yield one pot synthesis of 1-(2-methyl-8-aryl-substitued-imidazo[1,2-α]pyridin-3-yl)ethan-1-onefor the first-time. Subsequently, we performed <i>in silico</i> mode-of-action analysis and predicted that the synthesized imidazopyridines targets Phospholipase A₂ (PLA₂). <i>In vitro</i> analysis confirmed the predicted target PLA₂ for the novel imidazopyridine derivative1-(2-Methyl-8-naphthalen-1-yl-imidazo [1,2-α]pyridine-3-yl)-ethanone (compound <b>3f</b>) showing significant inhibitory activity towards snake venom PLA₂ with an IC₅₀ value of 14.3 μM. Evidently, the molecular docking analysis suggested that imidazopyridine compound was able to bind to the active site of the PLA₂ with strong affinity, whose affinity values are comparable to nimesulide. Furthermore, we estimated the potential for oral bioavailability by Lipinski's Rule of Five. Hence, it is concluded that the compound <b>3f</b> could be a lead molecule against snake venom PLA₂.</p></div

Structure of biologically active imidazo[1, 2-α]pyridines.

<p>Structure of biologically active imidazo[1, 2-α]pyridines.</p

Cyclocondensation of 5-alkyl/aryl-2-amino-1,3,4-thiadiazole (1a-j) with 1-adamantyl bromomethylketone to form (3a-j).

<p>Equimolar mixture of <b>1a-j</b>, and <b>2</b> was dissolved in 2 ml of [BMIM]⁺[BF₄]^- and the reaction was carried out in the presence of 0.1 equivalent of <b>Nano</b> MgO at 60 ⁰C.</p><p>Cyclocondensation of 5-alkyl/aryl-2-amino-1,3,4-thiadiazole (1a-j) with 1-adamantyl bromomethylketone to form (3a-j).</p

Computational binding mode analysis of AITs and <i>M</i>. <i>tubercolosis</i> CYP51.

<p>A) X-ray structure of CYP51 (green cartoon representation with heme cofactor as sticks with bound iron as brown sphere) in complex with a small molecule inhibitor (PDB: 2CIB). B) Similar interactions and an analogous three-dimensional arrangement are shown for compound <b>3f</b> of the AITs (cyan sticks). C) Overlay of the parent 1,3,4-thiadiazole of Oruc et al [Oruc04] with compound <b>3a</b> of the AITs. Positioning of ring centers, exit vectors, and overall shape are very similar, thereby plausibly explaining a similar bioactivity profile.</p

Structure of biologically active imidazo[1, 2-α]pyridines.

<p>Structure of biologically active imidazo[1, 2-α]pyridines.</p

Structure-activity relationships of newly synthesized tri-substituted-condensed-imidazopyridines.

<p>NS: Not Significant</p><p>Structure-activity relationships of newly synthesized tri-substituted-condensed-imidazopyridines.</p

Synthesis of tri-substituted-condensed-imidazopyridines.

<p>Synthesis of tri-substituted-condensed-imidazopyridines.</p

IC₅₀ values of imidazopyridine derivatives on <i>Vipera russelli</i> (RV) venom induced indirect haemolytic activity.

<p>RV venom (1 μg) was pre-incubated with different concentrations of imidazopyridine derivatives for 10 min at 37°C. Assay was performed as described in methods section and IC_<b>50</b> values for individual imidazopyridine derivatives obtained from dose response curve is presented.</p

A) Schematic representation of the preparation of AITs. B) ORTEP diagram of 3b.

<p>The compound crystallizes in a triclinic system under the space group P-1, and the benzyl imidazothiadiazole moiety adopts a chair conformation with the benzyl imidazothiadiazole moiety and the phenyl ring being bridged by the carbon atom (C6) with a dihedral angle of 69.73 degrees.</p