The room temperature electron paramagnetic resonance (EPR) spectrum of cis-diaquobis(1,1,1,5,5,hexafluoroacetylacetonato)manganese(II), Mn(hfa)2, and trans-diaquobis(1,1,1,5,5,5-hexafluoroacetylacetonato)manganese(II) hydrate, Mn(hfa)2·H2O, doped into a single crystal of the corresponding zinc(...

The mixed-ligand ruthenium(III) complexes with the following compositions were synthesized and isolated chromatographically: [Ru(acac)2(tfpb)], [Ru(acac)(tfpb)2], [Ru(acac)2(hfac)] and [Ru(dpm)2(hfac)] (acac−, 2, 4-pentanedionate ion; tfpb−, 4,4,4-trifluoro-1-phenyl-1,3-butanedionate ion; hfac−,...

Capillary electrochromatography was employed to separate the antibacterial 3-[4-(methylsulfinyl) phenyl]-5S-acetamidomethyl-2-oxazolidinone from its related S-oxidation products. The separation was optimized by a systematic search for the optimal separation conditions employing a modified centra...

Condensation of hexopyranosid-2-ulose 1 with nitromethane afforded after acetylation 2. Treatment with borohydride yielded stereoselectively 4. Reduction, acetylation, deblocking, and acid hydrolysis gave then C-2 branched N-acetylmannosamine 7 that was enzymatically converted to the first known...

As part of a program towards the development of specific inhibitors of human lysosomal β-hexosaminidase for use as chemical chaperones in therapy of GM2 gangliosidosis related diseases, the synthesis of 2-acetamidomethyl derivatives of isofagomine has been undertaken. Key event in this synthesi...

Design and synthesis of a few novel methylamino piperidinyl substituted oxazolidinones are reported. Their antibacterial activities have been evaluated in a MIC assay against broader panel of both susceptible and resistant Gram-positive strains. (S)-N-{3-[3-Fluoro-4-(methyl-{1-[3-(5-nitrofuran-2...

An amino acid based and bidentate Schiff base, (E)-methyl 2-((2-oxonaphthalen-1(2H)-ylidene)methylamino)acetate (ligand), was synthesized from the reaction of glycine-methyl ester hydrochloride with 2-hydroxy-1-naphthaldehyde. Characterization of the ligand was carried out using theoretical quan...

The growing evidence supporting a link between exposure to the naturally occurring toxin β-N-methylamino-l-alanine (BMAA) and progressive neurodegenerative diseases, has recently arisen the interest of the scientific community. Latest investigations suggest that dietary exposure to this algal t...

This letter presents synthesis and structure-activity relationship study of sulfonamide derivatives as inhibitors of Human Uric Acid Transporter 1 (hURAT1). Among all tested sulfonamide derivatives, compounds 9b, 16i and 19b exhibited excellent inhibition activity with IC50 value of 10, 2, and 8...

The 20S immunoproteasome (IP) is an interferon(IFN)-γ − and tumor necrosis factor (TNF) −inducible variant of the 20S constitutive proteasome (CP) in which all its peptidolytically active subunits β1, β2, and β5 are replaced by their cytokine inducible homologues β1i (LMP2), β2i (MECL-1), ...

A series of hypervalent selenium- and tellurium-containing compounds (organoselenuranes and organotelluranes) was evaluated aiming novel inhibitors of a threonine protease, namely the 20S proteasome (20S PT). In vitro assays demonstrated high inhibitory potency and specificity of these compounds...

Adaptive homeostasis enables rapid cellular signaling, leading to transcriptional and translational modifications (Davies, 2016) [1]. The Proteasome is one of the main cellular proteolytic enzymes that plays an essential role in the rapid clearance of oxidatively damaged cellular proteins, and i...

Proteasome-mediated degradation of proteins is a vital cellular process and is performed by the ubiquitin-dependent proteasome system (UPS) and the ubiquitin-independent proteasome system (UIPS). While both systems are necessary to maintain healthy cell function, many disease states are characte...

Proteasome deregulation has been related with several human diseases and, consequently, a detailed knowledge of its inhibition is essential for the design of efficient and selective drugs. The present paper is focused on the inhibition mechanism of proteasome 20S on the β5-subunit by dihydroepo...

The Hepatitis C virus (HCV) core protein plays a crucial role in the development of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Its involvement in these diseases is reportedly abolished by a knockout of the proteasome activator PA28γ gene in ...

The 20S proteasome is a large multisubunit proteolytic machine that is central to intracellular protein degradation. It is found in all three kingdoms of life and is ubiquitous in archaea and eukaryotes. Since its discovery, much effort employing a diverse array of structural biology methods has...

Interest in 5-S-cysteinyldopa (5-S-CD), a major excretion product of normal and malignant melanocytes, has traditionally concentrated on its significance as a biosynthetic precursor of pheomelanins, the characteristic pigments of red hair, and as a specific biochemical marker for monitoring mela...

The unstable quinones of 3,4-dihydroxyphenylalanine (dopa) and the most abundant cysteinyldopa isomers (2S-, 5S- and 2,5S,S′-) have been generated rapidly via disproportionation of their respective semiquinones prepared pulse radiolytically by one-electron oxidation of the corresponding dopas w...

Purpose: To evaluate the clinical significance of 5-S-cysteinyldopa (5-S-CD), a major intermediate in melanin synthesis, as a potential diagnostic tumor marker for uveal malignant melanoma.Methods: The levels of 5-S-CD in the serum were measured by high-performance liquid chromatography in 16 pa...

Under biologically relevant conditions, oxidation of 5-S-cysteinyldopa (1) to pheomelanins proceeds through the formation of the 1,4-benzothiazine 7 along with the 3-carboxy analogue 6 in much smaller amounts, as evidenced by isolation of the reduced forms 5 and 4 and by deuterium labelling expe...