Substituted benzoxazoles - synthesis and biological activity

There were 14 compounds prepaired, including 7 Schiff bases and 7 substitued benzoxazoles. The compounds were characterised by 1 H NMR, 13 C NMR, IR, TLC and by melting point. All the new compounds aren't described in Reaxys or in Chemical Abstracts, so they can be considered as original compounds. The reaction was done in two steps. First, the Schiff base was made by the condensation of proper aminophenol and benzaldehyde and in second step, the Schiff base was cyclized by lead (IV) acetate

Synthesis of human ω-O-acylceramides and evaluation of their effects on barrier properties of skin lipid membranes

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic chemistry Candidate: Mgr. Lukáš Opálka Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis of human ω-O-acylceramides and evaluation of their effects on barrier properties of skin lipid membranes The main objective of this work was to synthesize and study human acylceramides (acylCer, ceramides of the EO type) with the focus on the relationships between the acylCer concentration , structure of their polar head, their ability to form lamellar phases and permeability of model lipid membranes. Another objective was to synthesize ceramide-1-phosphates for the study of their signaling role in skin barrier and an analogue of ganglioside GM1 with shorter acyl chain as a standard for analysis of these lipids. Ceramides (Cer) belong to the family of sphingolipids. They are the central molecules in sphingolipid metabolism, they participate on cell regulatory processes and the formation of human skin lipid barrier. The main skin barrier is situated in the stratum corneum (SC), which is the uppermost layer of skin. The purpose of SC is to maintain homeostasis of the inner environment and to prevent the penetration of exogenous substances, allergens and bacteria to the..

Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation

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HILIC / ESI-MS stanovení gangliosidů a dalších tříd polárních lipidů v karcinomu ledvinových buněk a v normální tkáni.

Negative-ion hydrophilic liquid chromatography-electrospray ionization mass spectrometry (HILIC/ESI-MS) method has been optimized for the quantitative analysis of ganglioside (GM3) and other polar lipid classes, such as sulfohexosylceramides (SulfoHexCer), sulfodihexosylceramides (SulfoHex2Cer), phosphatidylglycerols (PG), phosphatidylinositols (PI), lysophosphatidylinositols (LPI), and phosphatidylserines (PS). The method is fully validated for the quantitation of the studied lipids in kidney normal and tumor tissues of renal cell carcinoma (RCC) patients based on the lipid class separation and the coelution of lipid class internal standard with the species from the same lipid class. The raw data are semi-automatically processed using our software LipidQuant and statistically evaluated using multivariate data analysis (MDA) methods, which allows the complete differentiation of both groups with 100% specificity and sensitivity. In total, 21 GM3, 28 SulfoHexCer, 26 SulfoHex2Cer, 10 PG, 19 PI, 4 LPI, and 7 PS are determined in the aqueous phase of lipidomic extracts from kidney tumor tissue samples and surrounding normal tissue samples of 20 RCC patients. S-plots allow the identification of most upregulated (PI 40:5, PI 40:4, GM3 34:1, and GM3 42:2) and most downregulated (PI 32:0, PI 34:0, PS 36:4, and LPI 16:0) lipids, which are primarily responsible for the differentiation of tumor and normal groups. Another confirmation of most dysregulated lipids is performed by the calculation of fold changes together with T and p values to highlight their statistical significance. The comparison of HILIC/ESI-MS data and matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) data confirms that lipid dysregulation patterns are similar for both methods.Pro kvantitativní analýzu gangliosidu (GM3) a dalších tříd polárních lipidů, jako jsou sulfohexosylceramidy (SulfoHexCer), sulfodihexosylceramidy (SulfoHex2Cer), fosfatidylglyceroly, byla optimalizována metoda hydrofilní interakční kapalinová chromatografie s detekcí pomocí hmotnostní spekrometrie a ionizací elektrosprejem (HILIC / ESI-MS). Metoda byla optimalizována pro kvantitativní analýzu (PG), fosfatidylinositoly (PI), lysofosfatidylinositoly (LPI) a fosfatidylseriny (PS). Metoda je plně validována pro kvantifikaci studovaných lipidů v ledvinové zdravé tkáni a nádorové tkáni pacientů s karcinomem ledvinných buněk (RCC) na základě separace tříd lipidů a koeluce vnitřního standardu se stejnou třídou lipidů. Surová data byla poloautomaticky zpracovány pomocí našeho softwaru LipidQuant a statisticky vyhodnocována metodami multivariační analýzy dat (MDA). Celkem bylo ve vodné fázi lipidomických extraktů tkání ledvinových nádorů a zdravé tkání stanoveno 21 GM3, 28 SulfoHexCer, 26 SulfoHex2Cer, 10 PG, 19 PI, 4 LPI a 7 PS. S-plot grafy umožňují identifikaci nejvíce upregulovaných (PI 40: 5, PI 40: 4, GM3 34: 1 a GM3 42: 2) a nejvíce downregulated (PI 32: 0, PI 34: a LPI 16: 0), které jsou primárně odpovědné za diferenciaci nádorových a normálních skupin. Další potvrzení většiny dysregulovaných lipidů se provádí výpočtem hodnot T a p pro určení jejich statistické významnosti. Srovnání údajů z HILIC / ESI-MS a matricové laserové desorpce (MALDI-MSI) potvrzuje, že modely lipidové regulace jsou podobné u obou metod

The intriguing molecular dynamics of Cer[EOS] in rigid skin barrier lipid layers requires improvement of the model

Omega-O-acyl ceramides such as 32-linoleoyloxydotriacontanoyl sphingosine (Cer[EOS]) are essential components of the lipid skin barrier, which protects our body from excessive water loss and the penetration of unwanted substances. These ceramides drive the lipid assembly to epidermal-specific long periodicity phase (LPP), structurally much different than conventional lipid bilayers. Here, we synthesized Cer[EOS] with selectively deuterated segments of the ultralong N-acyl chain or deuterated or 13C-labeled linoleic acid and studied their molecular behavior in a skin lipid model. Solid-state 2H NMR data revealed surprising molecular dynamics for the ultralong N-acyl chain of Cer[EOS] with increased isotropic motion toward the isotropic ester-bound linoleate. The sphingosine moiety of Cer[EOS] is also highly mobile at skin temperature, in stark contrast to the other LPP components, N-lignoceroyl sphingosine acyl, lignoceric acid, and cholesterol, which are predominantly rigid. The dynamics of the linoleic chain is quantitatively described by distributions of correlation times and using dynamic detector analysis. These NMR results along with neutron diffraction data suggest an LPP structure with alternating fluid (sphingosine chain-rich), rigid (acyl chain-rich), isotropic (linoleate-rich), rigid (acyl-chain rich), and fluid layers (sphingosine chain-rich). Such an arrangement of the skin barrier lipids with rigid layers separated with two different dynamic “fillings” i) agrees well with ultrastructural data, ii) satisfies the need for simultaneous rigidity (to ensure low permeability) and fluidity (to ensure elasticity, accommodate enzymes, or antimicrobial peptides), and iii) offers a straightforward way to remodel the lamellar body lipids into the final lipid barrier