Search results for "DISCOVERY"
showing 10 items of 4119 documents
Synthesis and radiosynthesis of N5-[18F]fluoroethyl-Pirenzepine and its metabolite N5-[18F]fluoroethyl-LS 75
2009
The well established M1 selective muscarinergic antagonist Pirenzepine 11-[2-(4-methyl-piperazin-1-yl)-acetyl]-5,11-dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (1) exhibits an unusual behaviour in vivo, which cannot be explained with M1 antagonism exclusively. One of the aspects discussed is a specific interaction with poly ADP-ribose polymerase (PARP-1). 1 undergoes metabolism to form LS 75 5,11-dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (2). In order to study deviations in Pirenzepine efficacy from pure M1 binding in vivo using PET, appropriate positron emitter labelled analogues of 1 and 2 were synthesised. Non-radioactive reference compounds 3 and 4 were tested for PARP-1 inh…
Stereoselective synthesis of 2-amino-1-hydroxy-3-phenylpropylphosphonic acid
1996
Abstract A highly stereoselective synthesis of 2-amino-1-hydroxy-3-phenylpropylphosphonic acid was achieved by simple addition of diethyl phosphite to enantiomeric N-blocked phenylalaninals. These compouds exhibit significant herbicidal activity.
Enantioselective Synthesis of Unsymmetrical Benzoins from (S)-Mandelic Acid Enolate and Aromatic Aldehydes.
2004
The reaction of the lithium enolate of the 1,3-dioxolan-4-one derived from optically active (S)-mandelic acid and pivalaldehyde with aromatic aldehydes proceeds readily to give the corresponding aldol products in good yields and diastereoselectivities. Subsequent hydroxyl protection, basic hydrolysis of the dioxolanone, oxidative decarboxylation of the α-hydroxyacid moiety, and hydroxyl deprotection provides chiral unsymmetrical benzoins with high enantiomeric excesses.
Anti-inflammatory drimane sesquiterpene lactones from an Aspergillus species
2014
Abstract IFN-γ inducible protein 10 (IP-10, CXCL10) is a 10 kDa chemokine, which is secreted from various cell types after exposure to pro-inflammatory stimuli. This chemokine is a ligand for the CXCR3 receptor and regulates immune responses by activating and recruiting leukocytes such as T cells, eosinophils, monocytes, and NK cells to sites of inflammation. Altered expression of CXCL10 has been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents a promising target for the development of new anti-inflammatory drugs. In a search for inhibitors of CXCL10 promoter activity, three structurally related drimane sesquiterpene lactones (compounds 1–3) were …
Atherosclerosis as an inflammatory disease.
2011
In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell type-specific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vasc…
Anti-inflammatory actions of the heme oxygenase-1 pathway.
2003
Heme oxygenase 1 (HO-1) is induced by oxidative or nitrosative stress, cytokines and other mediators produced during inflammatory processes, likely as part of a defence system in cells exposed to stress to provide a negative feedback for cell activation and the production of mediators, which could modulate the inflammatory response. HO-1 activity results in the inhibition of oxidative damage and apoptosis, with significant reductions in inflammatory events including edema, leukocyte adhesion and migration, and production of inflammatory cytokines. HO-1 is induced by nitric oxide (NO) in different biological systems and can control the increased production of this mediator observed in many i…
Taxonomic Identity, Geographic Distribution, and Commercial Exploitation of the Culinary-Medicinal Mushroom Pleurotus nebrodensis (Basidiomycetes)
2016
An updated overview of the outcome of studies conducted on the culinary-medicinal mushroom Pleurotus nebrodensis is presented by placing emphasis on the clarification of the taxonomic identity of P. nebrodensis and other related taxa possessing entirely white to cream basidiomes, which grow in association with different plants of the family Apiaceae. Cultivation techniques, quality of the product sold and sales price, as well as nutritional and medicinal aspects are discussed. Taking also into consideration the high economic importance of P. nebrodensis, it is essential to proceed with the verification of the commercial strains currently available in the international market under the name …
A review on the phytopharmacological studies of the genus Polygala
2020
Abstract Ethnopharmacological relevance The genus Polygala, the most representative genus of the Polygalaceae family, comprises more than 600 species from all over the world of which around 40 are distributed in China, some of them, being used in the Traditional Chinese Medicine system. Aim of the review We intend to discuss the current knowledge about the traditional uses, and the newest phytochemical and pharmacological achievements with tentative elucidation of the mechanism of action on the genus Polygala covering the period 2013–2019 to provide a scientific support to the traditional uses, and to critically analyze the reported studies to obtain new insights for further researches. Mat…
Sesterterpenes and macrolide derivatives from the endophytic fungus Aplosporella javeedii.
2020
Abstract Five sesterterpenes (1–5) including two new compounds (1 and 2), as well as a new (6) and a known macrolide (7) were isolated from the endophytic fungus Aplosporella javeedii. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and HRMS data as well as by comparison with the literature. Compound 4 and its acetyl derivatives 4a, 4b, 4c which were prepared by acetylation of 4 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 6.2 to 12.8 μM, respectively. Moreover, 4a and 4c exhibited also cytotoxicity against human leukemia (Jurkat J16) and lymphoma (Ramos) cell lines. Compound 7 showed strong …
Marine Isonitriles and Their Related Compounds.
2016
Marine isonitriles represent the largest group of natural products carrying the remarkable isocyanide moiety. Together with marine isothiocyanates and formamides, which originate from the same biosynthetic pathways, they offer diverse biological activities and in spite of their exotic nature they may constitute potential lead structures for pharmaceutical development. Among other biological activities, several marine isonitriles show antimalarial, antitubercular, antifouling and antiplasmodial effects. In contrast to terrestrial isonitriles, which are mostly derived from α-amino acids, the vast majority of marine representatives are of terpenoid origin. An overview of all known marine isoni…