ДО 80-РІЧЧЯ ВИДАТНОГО ВЧЕНОГО, ПЕДАГОГА ТА ГРОМАДСЬКОГО ДІЯЧА ІВАНА АНТОНОВИЧА МАЗУРА

The main scientific attainments of Ivan Mazur, Professor of Zaporizhzhya State Medical University, and his significant contribution to the development of pharmacy in Ukraine, in education of pharmaceutics in particular, is presented in the article.У статті висвітлюються основні наукові здобутки професора  Запорізького медичного університету професора Івана Мазура, відзначено його вагому роль у розвитку фармації України в цілому і фармацевтичної освіти, зокрема

SEEDS AND FLOWERS OF CHESTNUT TREES IN URBAN AREAS: A MUNICIPAL WASTE OR A RAW MATERIAL?

This study deals with the examination of total aescin content in flowers and seeds of Aesculus hippocastanum L. and Aesculus x carnea Hayne (Hippocastanaceae), collected in urban areas, as well as the content of Pb, Cd and Hg as an indicator of potential aerial pollution. Aescin identification was performed by TLC. Total aescin content was determined by UV-VIS spectrophotometry and HPTLC densitometry. The contents of Pb, Cd and Hg was determined by AAS. The concentration of aescin varied in a wide range between 0.17% (A. hippocastanum hulls) and 2.95% (A. hippocastanum cotyledons), as determined by spectrophotometric assay. Slightly lower results were recorded in HPTLC densitometry assay, ranging from 0,10% (the hulls of both plant species) to 2.39% (A. x carnea cotyledons). The extractable matter yield was between 5% and 26%, with a high share of total aescin (5% - 13%, depending on the source). The levels of Pb, Cd and Hg both in the plant material and the extracts remained low, indicating that the health safety of the plant specimens was not compromised. Our results suggest that the seeds and flowers of Chestnut trees in urban areas could be considered as a raw material for chemical and pharmaceutical industry in Serbia

A practical guide for using lithium halocarbenoids in homologation reactions

Lithium halocarbenoids are versatile reagents for accomplishing homologation processes. The fast α-elimination they suffer has been considered an important limitation for their extensive use. Herein, we present a series of practical considerations for an effective employment in the homologation of selected carbon electrophiles.© The Author(s) 201

Homologation of halostannanes with carbenoids: a convenient and straightforward one-step access to α-functionalized organotin reagents

A direct, single synthetic homologative transformation of halostannanes into mono- or di-substituted methyl analogues is documented. Critical for the success of the operation is the excellent nucleophilicity of carbenoid-like methyllithium reagents (LiCHXY, X, Y = halogen, OR, and CN): by simply individuating the reagents’ substitution pattern, the desired functionalized fragment is delivered to the electrophile. The wide scope of the protocol is evidenced also in the case of analogous halogermanium compounds. The tandem homologation–quenching with nucleophiles and the use of α-chloroallyllithium is also discussed

Evidence and isolation of tetrahedral intermediates formed upon the addition of lithium carbenoids to Weinreb amides and N-acylpyrroles

The tetrahedral intermediates generated upon the addition of halolithium carbenoids (LiCH2X and LiCHXY) to Weinreb amides have been intercepted and fully characterized as O-TMS heminals. The commercially available N-trimethylsilyl imidazole is the ideal trapping agent whose employment, combined with a straightforward neutral Alox chromatographic purification, enables the isolation of such labile species. The procedure could be advantageously extended also for obtaining O-TMS heminals from N-acylpyrroles. These intermediates manifest interesting reactivity including as precursors of more complex carbenoids

Homologation chemistry with nucleophilic α-substituted organometallic reagents: chemocontrol, new concepts and (solved) challenges

The transfer of a reactive nucleophilic CH2X unit into a preformed bond enables the introduction of a fragment featuring the exact and desired degree of functionalization through a single synthetic operation. The instability of metallated α-organometallic species often poses serious questions regarding the practicability of using this conceptually intuitive and simple approach for forming C–C or C–heteroatom bonds. A deep understanding of processes regulating the formation of these nucleophiles is a precious source of inspiration not only for successfully applying theoretically feasible transformations (i.e. determining how to employ a given reagent), but also for designing new reactions which ultimately lead to the introduction of molecular complexity via short experimental sequences

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.© 2017 Jansa et al

Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP

The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline. Up to now, due to the lack of a high-resolution X-ray structure of BSEP, in silico based identification of BSEP inhibitors focused on ligand-based approaches. In this study, we provide a homology model for BSEP, developed using the corrected mouse P-glycoprotein structure (PDB ID: 4M1M). Subsequently, the model was used for docking-based classification of a set of 1212 compounds (405 BSEP inhibitors, 807 non-inhibitors). Using the scoring function ChemScore, a prediction accuracy of 81% on the training set and 73% on two external test sets could be obtained. In addition, the applicability domain of the models was assessed based on Euclidean distance. Further, analysis of the protein–ligand interaction fingerprints revealed certain functional group-amino acid residue interactions that could play a key role for ligand binding. Though ligand-based models, due to their high speed and accuracy, remain the method of choice for classification of BSEP inhibitors, structure-assisted docking models demonstrate reasonably good prediction accuracies while additionally providing information about putative protein–ligand interactions.© The Author(s) 201

High-density lipoprotein sensor based on molecularly imprinted polymer

Decreased blood level of high-density lipoprotein (HDL) is one of the essential criteria in diagnosing metabolic syndrome associated with the development of atherosclerosis and coronary heart disease. Herein, we report the synthesis of a molecularly imprinted polymer (MIP) that selectively binds HDL, namely, HDL-MIP, and thus serves as an artificial, biomimetic sensor layer. The optimized polymer contains methacrylic acid and N-vinylpyrrolidone in the ratio of 2:3, cross-linked with ethylene glycol dimethacrylate. On 10 MHz dual electrode quartz crystal microbalances (QCM), such HDL-MIP revealed dynamic detection range toward HDL standards in the clinically relevant ranges of 2–250 mg/dL HDL cholesterol (HDL-C) in 10 mM phosphate-buffered saline (PBS, pH = 7.4) without significant interference: low-density lipoprotein (LDL) yields 5% of the HDL signal, and both very-low-density lipoprotein (VLDL) and human serum albumin (HSA) yield 0%. The sensor reveals recovery rates between 94 and 104% at 95% confidence interval with precision of 2.3–7.7% and shows appreciable correlation (R 2 = 0.97) with enzymatic colorimetric assay, the standard in clinical tests. In contrast to the latter, it achieves rapid results (10 min) during one-step analysis without the need for sample preparation.© The Author(s