Home About us Contact
|
Home About us Contact | ||
|
|
||
Active Derivatives (active + derivative)
Selected Abstracts9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic proteinJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Hui Shen Abstract Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia-induced injury, and these effects involve BMPs. © 2008 Wiley-Liss, Inc. [source] Synthesis and NMR spectroscopic studies of optically active derivatives of ,-aminobutenoic acids and 2-amino-pyrrolin-4-onesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2001Margarita Petroliagi An efficient method for the preparation of optically active derivatives of ,-amino-butenoic acids and their cyclic derivatives, 2-amino-pyrrolin-4-ones, from ,-amino acids is described. Partial racemization accompanies the formation of initial unsaturated ,-amino-,-hydroxy esters 5,8, as determined by chiral HPLC. [source] Therapeutic potential of sulfamides as enzyme inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 6 2006Jean-Yves Winum Abstract Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, ,-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HNSO2NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications. © 2006 Wiley Periodicals, Inc. Med Res Rev [source] Synthesis and Anticancer Activity of Novel Betulinic acid and Betulin DerivativesARCHIV DER PHARMAZIE, Issue 8 2010Harish Kommera Abstract A series of novel betulinic acid derivatives 3,11 and betulin derivatives 12,17 were synthesized. The compounds were characterized by the means of 1H- and 13C-NMR spectroscopy as well as mass spectrometry. The compounds have been tested on ten tumor cell lines of different histogenic origin. The most active derivatives, containing a chloroacetyl group on C-3 in betulinic acid 9 and C-28 in betulin 15, were up to ten times more cytotoxic and many fold more selective towards tumor cells in comparison to normal cells (fibroblasts) than betulinic acid. Furthermore, compound 15 was found to possess cell growth inhibition even when treated for a short time on anaplastic thyroid cancer cells (SW1736). [source] Asymmetric Desymmetrization Based on an Intramolecular Haloetherification: A Highly Effective and Recyclable Chiral Nonracemic Auxiliary, 2- exo -Methyl-3- endo -phenyl-5-norbornene-2-carboxaldehyde, for meso -1,3- and meso -1,4-DiolsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2004Hiromichi Fujioka Prof. Dr. Abstract A new chiral auxiliary, a 3- endo -phenyl norbornene aldehyde derivative, which is a crystalline, very stable, and easily handled, was developed for the desymmetrization of meso -1,3- and meso -1,4-diols. The key step of the method, an intramolecular bromoetherification, proceeded in a highly diastereoselective manner. A four-step sequence, 1) acetalization, 2) intramolecular bromoetherification followed by acid hydrolysis, 3) protection of the alcohol, and 4) retrobromoetherification, transformed the meso -diols into optically active derivatives. The 3- endo -phenyl norbornene aldehyde derivative was simultaneously reformed and could be used repeatedly. This is the first chemical example of a single auxiliary that is applicable for highly enantioselective desymmetrization of meso -1,3- and meso -1,4-diols; to the best of our knowledge, this is the best chemical method available for the desymmetrization of meso -1,4-diols. [source] Computational Studies to Discover a New NR2B/NMDA Receptor Antagonist and Evaluation of Pharmacological ProfileCHEMMEDCHEM, Issue 10 2008Rosaria Gitto Prof. Abstract The ionotropic glutamate NMDA/NR2B receptor and its interaction with ifenprodil-like noncompetitive ligands were investigated by a combined ligand-based and target-based approach. First, we generated 3D pharmacophore hypotheses and identified common chemical features that are shared by a training set of well-known NR2B antagonists. The binding mode of the most representative ligand was also studied by molecular docking. Because the docking results and the suggested 3D pharmacophore model were in good agreement, we obtained new information about the NR2B ifenprodil site. The best pharmacophoric hypothesis was used as a query for in,silico screening; this allowed the identification of new "hit". We synthesized "hit-compound" analogues, and some of the molecules showed significant activity both in binding and functional assay as well as in,vivo anticonvulsant efficacy in DBA/2 mice. The most active derivatives also exhibited neuroprotective effects against glutamate-induced toxicity in HCN-1A cells. [source] | ||||||||||