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Synthetic Derivatives (synthetic + derivative)
Selected AbstractsThe Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004Claudia Link Abstract A 2-kDa synthetic derivative of the macrophage-activating lipopeptide (MALP-2) from Mycoplasma fermentans is a potent inducer of monocytes/macrophages and improves the immunogenicity of antigens co-administered by systemic and mucosal routes. Dendritic cells (DC) are the most potent antigen-presenting cells, which are able to prime naive T cells in vivo. To elucidate the underlying mechanisms of MALP-2 adjuvanticity, we analyzed its activity on bone marrow-derived murine DC. In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules. MALP-2 also enhances the secretion of cytokines (IL-1,, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells. Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity. Thus, the adjuvanticity of MALP-2 can be mediated, at least in part, by the stimulation of DC maturation, which in turn leads to an improved antigen presentation. Therefore, MALP-2 is a promising molecule for the development of immune therapeutic or prophylactic interventions. [source] Ivermectin: pharmacology and application in dermatologyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2005Assen L. Dourmishev Ivermectin is a synthetic derivative of the antiparasitic class of compounds known as avermectins. It is a macrolide endectocide with activity against both endoparasites with cutaneous tropism (Strongyloides stercoralis, Ancylostoma braziliense, Cochliomyia hominivorax, Dermatobia hominis, Filaria bancrofti, Wucheria malayi, Onchocerca volvulus, Loa-loa) and ectoparasites such as Sarcoptes scabies, Pediculus humanus, Demodex folliculorum, and Cheyletiella sp. Ivermectin is of great interest in the treatment of patients with different forms of scabies, head lice, demodecidosis, cutaneous larva migrans, cutaneous larva currens, myiasis, and filariasis. [source] Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L -leucine in high-cholesterol fed ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2005Soon-Ja Kim Abstract A preliminary study revealed that 3,4-di(OH)-hydrocinnamate (HC), a polyphenolic compound, lowered the plasma lipids in high-cholesterol fed rats. Accordingly, this study was designed to test the lipid-lowering efficacy of a synthetic derivative, 3,4-di(OH)-phenylpropionic (L -leucine) amide (PPLA), in rats fed a high-cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to a high-cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The supplementation of HC and PPLA significantly lowered the plasma and hepatic cholesterol and triglyceride levels compared to the control group. The activities of hepatic HMG-CoA reductase (164 ± 9.12 and 124.74 ± 17.09 pmol/min/mg protein vs. 245.41 ± 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 ± 11.48 and 334.35 ± 17.68 pmol/min/mg protein vs. 490.41 ± 16.69 pmol/min/mg protein, p < 0.05) were significantly lower in the HC- and PPLA-supplemented groups than in the control group. However, PPLA was more effective in inhibiting the enzyme activities than HC. The excretion of neutral sterol was significantly higher in HC- and PPLA-supplemented groups than in the control group. Therefore, these results indicate that PPLA, a leucine-attached version of HC, exhibited a similar significant hypocholesterolemic effect to HC in rats fed a high-cholesterol diet. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:25,31, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20054 [source] The use of desmopressin as a hemostatic agent: A concise reviewAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2007Massimo Franchini Desmopressin, a synthetic derivative of the antidiuretic hormone vasopressin, is the treatment of choice for most patients with von Willebrand disease and mild hemophilia A. Moreover, the compound has been shown to be useful in a variety of inherited and acquired hemorrhagic conditions, including some congenital platelet function defects, chronic liver disease, uremia, and hemostatic defects induced by the therapeutic use of antithrombotic drugs such as aspirin and ticlopidine. Finally, desmopressin has been used as a blood saving agent in patients undergoing operations characterized by large blood loss and transfusion requirements, but studies suggest that this is not as effective as other methods. This review briefly summarizes the current clinical indications on the use of desmopressin as a hemostatic agent. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Molecular interactions of isoxazolcurcumin with human serum albumin: Spectroscopic and molecular modeling studiesBIOPOLYMERS, Issue 2 2009Bijaya Ketan Sahoo Abstract Curcumin is a nontoxic natural product with diverse pharmacological potencies. We report the interaction of a potent synthetic derivative of curcumin, isoxazolcurcumin (IOC) with human serum albumin (HSA) using various biophysical methods. The observed fluorescence quenching of HSA by IOC is due to a complex formation by a static quenching process with a quenching constant of the order of 105M,1. The binding affinity and the number of binding sites were obtained from a Scatchard analysis. Thermodynamics reveals that the interaction is entropy driven with predominantly hydrophobic forces. From the observed Förster-type fluorescence resonance energy transfer (FRET), the donor (Trp 214 in HSA) to acceptor (IOC) distance is calculated to be 3.2 nm. The conformational changes of HSA due to the interaction were investigated qualitatively from synchronous fluorescence spectra along with a quantitative estimation of the secondary structure from Fourier Transform Infrared (FTIR) and circular dichroism (CD) spectroscopies. Molecular docking studies were performed to obtain information on the possible residues involved in the interaction process, and changes in accessible surface area of the interacting residues were calculated. The preferred binding site of IOC was analyzed by ligand displacement experiments with 1-anilino-8-naphthalenesulfonate (ANS) and warfarin-bound HSA. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 108,119, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Multifunctional host defense peptides: antiparasitic activitiesFEBS JOURNAL, Issue 22 2009Amram Mor Whereas significant knowledge is accumulating on the antibacterial and antifungal properties of host defense peptides (HDPs) and their synthetic mimics, much less is known of their activities against parasites. A variety of in vitro and in vivo antiparasitic assays suggest that these notorious antimicrobial compounds could represent a powerful tool for the development of novel drugs to fight parasites in the vertebrate host or to complement current therapeutic strategies, albeit the fact that HDPs essentially act by nonspecific mechanisms casts serious doubt on their ability to exert sufficient selectivity to be considered ideal candidates for drug development. This minireview summarizes recent efforts to assess the antiparasitic properties of HDPs and their synthetic derivatives, focusing on two of the most used models ,Plasmodium and Leishmania species , for antiparasitic assays against the different development stages. [source] Anti-inflammatory activity of the synthetic C-C biflavonoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2006Haeil Park To find anti-inflammatory agents based on plant constituents, the effects of six synthetic C-C biflavonoids connecting with different positions of C-C bond between flavone monomers (a: 4,-4,, b: 4,-3,, c: 4,-6, d: 3,-6, e: 6-6, f: 4,-3) were examined on PGE2 and nitric oxide (NO) production from lipopolysaccharide (LPS)-treated macrophages, RAW 264.7. Among the compounds tested, the biflavonoids d, e, and f showed a considerable inhibition of cyclooxygenase-2 (COX-2)-mediated PGE2 production at concentrations up to 50 ,M, while the derivative c exerted cytotoxic effects on RAW cells. Especially, the biflavonoid e possessed the most potent inhibitory activity of PGE2 production with an IC50 of 3.7 ,M, compared with an IC50 of 8.2,20.7 ,M by ginkgetin (natural biflavonoid). Western blot and reverse transcriptase-polymerase chain reaction analyses have shown that the inhibition of PGE2 production by these synthetic derivatives was mediated at least in part by COX-2 inhibition, but not by COX-2 down-regulation. Meanwhile, these synthetic biflavonoids did not considerably inhibit inducible nitric oxide synthase-mediated NO production at concentrations up to 50 ,M. When intraperitoneally administered, the biflavonoid e showed a significant anti-inflammatory activity (22.2% inhibition) against rat carrageenan-induced paw oedema at 5 mg kg,1. The biflavonoid e may be used as a synthetic lead for developing new anti-inflammatory agents. [source] 13C and 1H NMR signal assignments of some new synthetic dehydroabietic acid derivativesMAGNETIC RESONANCE IN CHEMISTRY, Issue 4 2008Marinaldo S. de Carvalho Abstract The 1H and 13C NMR signal assignments of a series of new synthetic derivatives of dehydroabietic acid are presented. Copyright © 2008 John Wiley & Sons, Ltd. [source] Flavonoids as RTK inhibitors and potential anticancer agentsMEDICINAL RESEARCH REVIEWS, Issue 5 2008Florence Teillet Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715,745, 2008 [source] The skimmiwallinols,minor components of the epicuticular wax of Cocos nucifera,PHYTOCHEMICAL ANALYSIS, Issue 3 2007Fabiola Escalante-Erosa Abstract Four new skimmiwallinol derivatives, isoskimmiwallinol acetate (4), skimmiwallinol acetate (5), isoskimmiwallinone (6) and skimmiwallinone (7), along with the previously isolated major components isoskimmiwallin (2) and skimmiwallin (3), have been found in the wax extract of pinnae from Cocos nucifera. Metabolites 4 and 5 were obtained as an inseparable mixture and identified by analysis of spectroscopic data and chemical correlation with 2 and 3, respectively. Metabolites 6 and 7 were identified by GC co-injection with the corresponding synthetic derivatives prepared from 4 and 5. Copyright © 2007 John Wiley & Sons, Ltd. [source] Design, Synthesis, and Biological Evaluation of New Territrem B AnaloguesCHEMISTRY & BIODIVERSITY, Issue 4 2005Xiangrui Jiang Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined. [source] In the Quest for a Virtual Pseudo Receptor for Sandalwood-Like Odorants.CHEMISTRY & BIODIVERSITY, Issue 7 2004Based on similarities between naturally occurring (,)-(Z)- , - or (+)-(Z)- , -santalol ((,)- 1 or (+)- 2, resp.) and the reversed (E)-configured synthetic derivatives from campholenal (7a), a simple model A was developed. Besides reconciliation of this stereochemical aspect, this initial model also tentatively explained the enantiodiscriminations as well as the large spectra of distances separating the OH function from the lipophilic quaternary center(s) reported for different classes of substrates. Evolution, modifications, and refinement of this imperfect model allied with the research for alternative possibilities are illustrated, along with a historical guideline, in the light of olfactively challenging synthetic seco-substructures as well as literature reports. Despite evolution of the inadequate model A and a plausible interpretation of the lipophilic part, the topological positions of the OH function and its vicinal alkyl substituent could nevertheless not be fully ascertained by this approach. This apparently inconclusive empirical concept prompted us to turn our attention towards a computerized methodology, which will constitute the second and third part of this study. [source] Natural alkaloids and synthetic relatives as chiral templates of the Orito's reactionCHIRALITY, Issue 1 2010Emília Tálas Abstract The enantioselective hydrogenation of methyl or ethyl pyruvate over cinchona-platinum catalyst system (Orito's reaction) is one of the most intensively studied heterogeneous catalytic asymmetric hydrogenation reactions. Studies aiming at systematic changes of the chiral template have played a crucial role in creating hypotheses for the mechanism of Orito's reaction. It is very important to clarify which structural unit of the alkaloid takes part in the enantiodifferentiation, and learn about the role of the different structural units of chiral templates. In this article, we made an attempt to describe the behavior of natural alkaloids, their synthetic derivatives, and analogues as chiral templates in the heterogeneous catalytic asymmetric hydrogenation of activated ketones. Chirality, 2010. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||