Unique PFK regulatory property from some mosquito vectors of disease, and from Drosophila melanogaster

Effect of F2, 6BP on Aedes aegypti PFK activity. PFK activity was measured at pH = 7.4, 1 mM F6P, 5 mM ATP at several F2, 6BP concentrations (0.01–50 μM). Values are the means ± SEM of three independent experiments. (TIF 466 kb

沿岸海洋景観のGISデータベースの構築

<p>Superimposition of the top poses of LASSBio-448 obtained by docking with PDE4A and PDE4C (light purple surface, PDE4A) (A), PDE4B and PDE4D (gold surface, PDE4D) (B). Hydrogen atoms have been omitted for clarity.</p

Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators

Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERa ligands and as inhibitors of estrogen-stimulated proliferation of MCF-7 breast cancer cells. The conformations of each analogue, sampled from a molecular dynamics simulation, were placed in a grid cell lattice according to three trial alignments, considering two grid cell sizes (1.0 and 2.0 Å). The QSAR equations, generated by a combined scheme of genetic algorithms (GA) and partial least squares (PLS) regression, were evaluated by “leave-one-out” cross-validation, using a training set of 41 compounds. External validation was performed using a test set of 13 compounds. The obtained 4D-QSAR models are in agreement with the proposed mechanism of action for raloxifene. This study allowed a quantitative prediction of compounds’ potency and supported the design of new raloxifene analogs

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-alpha production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. (c) 2012 Elsevier Masson SAS. All rights reserved.CNPqCNPqFAPERJFAPERJCAPESCAPESINCTINOFARINCT-INOFAR [573.564/2008-6, E-26/170.020/2008

Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.

<p>Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.</p

Examples of PDE4 inhibitors of first and second generations.

<p>Examples of PDE4 inhibitors of first and second generations.</p