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Inner Salt (inner + salt)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	50%

Selected Abstracts

Vorinostat enhances the antimyeloma effects of melphalan and bortezomib

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
Richard A. Campbell
Abstract Objectives:, Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. Methods:, RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferation was measured using the MTS [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfphophenyl)-2H-tetrazolium, inner salt] assay. Severe combined immunodeficient mice bearing LAG,-1B tumors were treated with vorinostat [30, 60, or 100 mg/kg daily for five consecutive days per week (qd×5d), 100 or 300 mg/kg daily for 2 d/wk (qd×2d)], melphalan (1, 3, or 10 mg/kg qd×1d), bortezomib (0.25 or 0.5 mg/kg qd×2d), or combinations thereof for 35 d. Tumor growth was determined via measurement of human immunoglobulin G (hIgG) levels and tumor volume. Results and Conclusions:, Vorinostat enhanced the anti-MM effects of melphalan and bortezomib in vitro. Synergism was observed with vorinostat and melphalan in RPMI8226 and U266 cell lines. Vorinostat 100 mg/kg in combination with melphalan 3 mg/kg resulted in significant inhibition of tumor growth in vivo, compared with control (tumor volume P = 0.0001; hIgG P = 0.0001), single-agent vorinostat (tumor volume P = 0.0025; hIgG P = 0.0137), and single-agent melphalan (tumor volume P = 0.0043; hIgG P = 0.0426). Vorinostat also enhanced the antimyeloma effects of bortezomib in vivo. Vorinostat enhances the anti-MM activity of melphalan and bortezomib in vitro and in vivo. This study provides rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment of MM. [source]

c-Jun NH2 -terminal kinase-dependent fas activation contributes to etoposide-induced apoptosis in p53-mutated prostate cancer cells

THE PROSTATE, Issue 4 2003
Keiji Shimada
Abstract Background The death receptor, Fas, has recently been demonstrated to contribute the chemotherapeutic agents-induced apoptosis, however, the detail mechanisms have yet to be fully understood, especially in prostate cancer cells. Methods PC-3 and DU145 stably transfected with dominant negative form of Fas-associated death domain (FADD) or specific kinase of c-Jun NH2 -terminal kinase (JNK) (mitogen-activated protein kinase kinase, MKK7) were selected in the presence of hygromycin B (Hyg B). Cell viability was examined by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphonyl)- 2H-tetrazolium, inner salt (MTS) assay or flowcytometric analysis using green fluorescent protein (GFP). Apoptosis was examined by DNA ladder, Western blotting analysis of cleaved caspases, or morphological analysis. The expression of Fas and JNK activation were investigated by Western blotting/flowcytometric analysis and in vitro kinase assay, respectively. Results Stimulation with etoposide significantly up-regulated Fas, and the death-inducing signaling complex (DISC) was formed in PC-3 and DU145. Stable transfection with dominant-negative FADD inhibited etoposide-induced apoptosis. In addition, stable transfection with dominant-negative MKK7, by which JNK activation was inhibited, canceled both the up-regulation of Fas and the formation of DISC by etoposide. Re-introduction of wild type p53 into PC-3 and DU145 completely suppressed these inhibitory effects. Conclusions These results suggest that, in p53-mutated prostate cancer, JNK-initiated Fas-mediated apoptotic signals may play an important role in chemosensitivity. Prostate 55: 265,280, 2003. © 2003 Wiley-Liss, Inc. [source]

New Uses for the Burgess Reagent in Chemical Synthesis: Methods for the Facile and Stereoselective Formation of Sulfamidates, Glycosylamines, and Sulfamides

CHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2004
K. C. Nicolaou Prof.
Abstract Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide, inner salt) has found significant use in chemical synthesis as a dehydrating agent, almost no work has been directed towards its potential in other synthetic applications. As this article will detail, we have found that the Burgess reagent is remarkably effective at accomplishing a number of non-dehydrative synthetic tasks when applied to appropriate substrates, such as the formation of sulfamidates from 1,2-diols or epoxyalcohols, ,- and ,-glycosylamines from carbohydrates, and cyclic sulfamides from 1,2-aminoalcohols. Beyond delineating the power of these new reaction manifolds, we also describe the construction of a group of alternative Burgess-type reagents that extends the scope of these new reactions even further. [source]

Betaine Adducts of N-Heterocyclic Carbenes: Synthesis, Properties, and Reactivity

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 13 2009
Lionel Delaude
Abstract N-Heterocyclic carbenes (NHCs) form stable zwitterionicadducts with a range of heteroallenes, ketenes, and allenes. Although the first representatives of this class of inner salts were first investigated as far back as the 1960s, they have enjoyed a sustained interest from the chemical community over the years. Depending on the nature of their anionic moiety, NHC betaines display a very broad palette of reactivities and have found applications in various fields of organic synthesis and catalysis. In this Microreview, the synthesis, properties, and reactivity of NHC betaines are surveyed. The NHCs under consideration include ylidenes derived from imidazole, benzimidazole, imidazoline, thiazole, or triazole, and the heteroallenes investigated so far are carbon dioxide, carbon disulfide, isocyanates, isothiocyanates, and their selenium analogues. A historical background is provided for each type of adduct under consideration, but emphasis is placed mainly on developments that have appeared in the literature within the past few years. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]