Search results for "Amides"
showing 10 items of 552 documents
Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: Possible involvement of the COX-2 metabolite prostamide E 2
2007
The eCB [endoCB (cannabinoid)] system is being considered as a novel therapeutic target for immune disorders. Cytokines of the IL-12 (interleukin-12) family have essential functions in cell-mediated immunity. In the present study, we have addressed the mechanisms of action of the eCB AEA (anandamide) on the regulation of IL-12p40 in activated microglia/macrophages. We demonstrated that AEA can inhibit the expression of p35, p19 and p40 subunits, which form the biologically-active cytokines IL-12 and IL-23 in microglia stimulated with LPS (lipopolysaccharide)/IFNγ (interferon γ). Additionally, we have provided evidence that AEA reduces the transcriptional activity of the IL-12p40 gene in LPS…
Systematic Modulation of the Supramolecular Gelation Properties of Bile Acid Alkyl Amides
2018
The self-assembly properties of nine low-molecular-weight gelators (LMWGs) based on bile acid alkyl amides were studied in detail. Based on the results, the number of hydroxyl groups attached to the steroidal backbone plays a major role in the gelation, although the nature of the aliphatic side chain also modulates the gelation abilities. Of the 50 gel systems studied, 35 are based on lithocholic acid and 15 on cholic acid derivatives. The deoxycholic acid derivatives did not form any gels. The gelation occurred primarily in aromatic solvents and the gels manifested typical fibrous or spherical morphologies. The 13C cross-polarized magic angle spinning (CPMAS) NMR spectra measured on the cr…
Bile acid alkylamide derivatives as low molecular weight organogelators: systematic gelation studies and qualitative structural analysis of the syste…
2011
A series of amino- and hydroxyalkyl amides of bile acids have been synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), (1)H and (13)C nuclear magnetic resonance spectroscopy (NMR), as well as electrospray ionization mass spectrometry (ESI-MS) measurements. The ability of the synthesized molecules to promote gel formation was systematically investigated. Out of 396 combinations formed by 11 compounds and 36 different solvents, 22 gel-containing systems were obtained with 1% (w/v) gelator concentration. Apart from one exception, the gelator compounds were lithocholic acid derivatives. This challenges the general trend of bile acid-based physical gelators, accordin…
The antifibrotic potential of a sustained release formulation of a PDGF beta-receptor targeted rho kinase inhibitor
2019
Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production and portal hypertension in liver cirrhosis. Inhibition of rho kinase activity can reduce these activities, but may also lead to side effects, for instance systemic hypotension. This can be circumvented by liver-specific delivery of a rho kinase inhibitor to effector cells. Therefore, we targeted the rho kinase inhibitor Y27632 to the key pathogenic cells in liver fibrosis, i.e. myofibroblasts including activated HSCs that highly express the PDGF beta-receptor, using the drug carrier pPB-MSA. This carrier consists of mou…
Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer
2014
Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differen…
New amide and dioxopiperazine derivatives from leaves of Breynia nivosa
2017
The first chemical investigation of leaves of Breynia nivosa from Nigeria resulted in the isolation of two new amide derivatives breynivosamides A and B (1 and 2) and two new dioxopiperazine derivatives breynivosines A and B (4 and 5) together with seven known compounds (3, 6-11). The structures of the new compounds were elucidated by 1D, 2D NMR and HRESIMS data as well as by comparison with the literature. All isolated compounds were tested for the cytotoxic and antimicrobial activities. Only cristatin A (6) showed cytotoxicity against the L5178Y mouse lymphoma cell line with an IC50 value of 13.9μM while breynivosamide A (1) exhibited moderate antimicrobial activity against Mycobacterium …
The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.
2011
Lung cancer is a malignant disease with poor outcome, which has led to a search for new therapeutics. The PI3K/Akt/mTOR and Ras/raf/Erk pathways are key regulators of tumor growth and survival. In the present study, their roles were evaluated by MTT assay, flow cytometry and Western blotting in lung cancer cells. We found that a high efficacy of antitumor activity was shown with GDC-0941 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In addition, H460 cells with activating mutations of PIK3CA were relatively more sensitive to GDC-0941 than A549 cells with wild-type PIK3CA. Furthermore, GDC-0941 was highly efficacious in combination with U0…
Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor ce…
2010
Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex®) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependen…
3,5-Diaizvietotu-4-fenil-2-pirolidonu un to strukturālo analogu sintēze
2017
5-Alkil-4-fenil-3-metilēn-2-pirolidonu un to strukturālo analogu sintēze. Baškevičs V., Darba vadītājs: Dr. ķīm. Maksims Vorona. Maģistra darbs. 102 lappuses, 18 attēli, 30 pielikumi, 32 literatūras avoti. Latviešu valodā. Uz Morita-Baylis-Hillman reakcijas produktu bāzes realizēta to acilēšana un nitroalkānu pievienošanas starpproduktam. Iegūtie starpprodukti tika pakļauti reducēšanas reakcijai un iekšmolekulārai ciklizācijai ar eksometilēn grupu saturošo 2-pirolidonu veidošanu. Šim nolūkam bija izmēģinātas vairākas literatūrā eksistējošas 5-alkil-4-fenil-3-metilēn-2-pirolidonu iegūšanas metodes, no kuriem tika izvēlēta reducēšanas reakcija ar dzelzs pulvera palīdzību ledus etiķskābē. Iegū…
Spectral and microscopic study of self-assembly of novel cationic spermine amides of betulinic acid
2016
Supramolecular characteristics of two spermine amides of betulinic acid (1 and 2) were studied by measuring and evaluating their UV-VIS-NIR spectra in aqueous acetonitrile and DOSY-NMR spectra in tetradeuteromethanol, accompanied by atomic force microscopy (AFM) images, scanning electron microscopy (SEM) micrographs, and transmission electron microscopy (TEM) micrographs. Fibrous supramolecular self-assembly of 1 and 2 was observed by AFM images, as well as by the SEM and TEM micrographs. Bathochromic shifts of the absorbance maximum at 870nm to 1015-970nm in the UV-VIS-NIR spectra were observed with increasing water content in the acetonitrile/water systems, indicating formation of fibrous…