Determinarea toxicităţii acute a unor noi compuşi chimici cu proprietăţi antituberculoase

La Institutul de Chimie al AŞM au fost sintetizaţi compusi, principalele substanţe active ale cărora reprezintă derivaţi ai oxadiazolilor. Datele preliminare ale testărilor in vitro au determinat activitatea inhibitorie asupra creşterii coloniilor M.tuberculosis. În cadrul proiectului „De la compuşi naturali la analogii lor şi spre evaluarea preclinică a noilor compuşi cu proprietăţi antituberculoase” la Centrul Ştiinţific al Medicamentului al IP USMF „Nicolae Testemiţanu” a fost evaluată toxicitatea acută a 7 compuşi sintetizaţi. Pentru compuşii MF51, MF14 s-a constatat toxicitatea minimă, ei fiind plasaţi în clasa de toxicitate 5 conform TG 423 Acute Toxic Class Method (OECD)

Cyclodextrins in Asymmetric and Stereospecific Synthesis

Since their discovery, cyclodextrins have widely been used as green and easily available alternatives to promoters or catalysts of different chemical reactions in water. This review covers the research and application of cyclodextrins and their derivatives in asymmetric and stereospecific syntheses, with their division into three main groups: (1) cyclodextrins promoting asymmetric and stereospecific catalysis in water; (2) cyclodextrins’ complexes with transition metals as asymmetric and stereospecific catalysts; and (3) cyclodextrins’ non-metallic derivatives as asymmetric and stereospecific catalysts. The scope of this review is to systematize existing information on the contribution of cyclodextrins to asymmetric and stereospecific synthesis and, thus, to facilitate further development in this direction

CYCLODEXTRINS – FIELDS OF APPLICATION. PART I

This review is dedicated to different fields of use of cyclodextrins, a family of three cyclic natural oligosaccharides and their derivatives. The first part of the review gives a brief description of the main and the most recent developed applications of cyclodextrins in food, cosmetic industry, environmental protection technologies and agriculture. Different products based on inclusion complexes with cyclodextrins and technologies with different use of cyclodextrins and inclusion complexes are described

ROLE OF CYCLODEXTRINS IN NEW ANTIMYCOBACTERIAL FORMULATIONS

This paper is dedicated to the role of cyclodextrins in new formulations for the treatment of infections with Mycobacterium tuberculosis that are in the process of design and development. Cyclodextrins play the role of solubilizing agents and promoters of the antimycobacterial substances penetration inside the mycobacterial cell. Different formulations and their advantages and disadvantages are discussed

SPECTROPHOTOMETRIC STUDIES OF SANGUINARINE-Β-CYCLODEXTRIN COMPLEX FORMATION

The main aim of this study was to investigate the influence of pH and the presence of hydrophilic polymer polyvinylpyrrolidone on the formation of sanguinarine-β-cyclodextrin (SANG-β-CD) inclusion complex. Spectrophotometric studies of the SANG-β-CD systems in the presence and without 0.1 % PVP at the pH 5.0 did not show any evidence of the complex formation. However, the same systems showed several obvious evidences at the pH 8.0: the hyperchromic and the hypochromic effects and the presence of the isosbestic point in the region of 200 – 210 nm. The association constants calculated by three linear methods: Benesi-Hildebrand, Scott and Scatchard, were two times higher for the systems with addition of 0.1% PVP than for the systems without it

Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents

Streicher, Felix/0000-0002-8375-2958; Klein, Christian/0000-0003-3522-9182; Richter, Michael/0000-0002-8227-0543; Bartenschlager, Ralf/0000-0001-5601-9307WOS: 000458933200005PubMed: 30605241Recent studies indicate that tubulin can be a host factor for vector-borne flaviviruses like dengue (DENV) and Zika (ZIKV), and inhibitors of tubulin polymerization such as colchicine have been demonstrated to decrease virus replication. However, toxicity limits the application of these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed by the esterase in vitro. In contrast to previous reports, the phenylglycine esters were not cleaved by human carboxylesterase. The antiviral activity of combretastatin, colchicine, and selected prodrugs against DENV and ZIKV in cell culture was observed at low micromolar and sub-micromolar concentrations. In addition, docking studies were performed to understand the binding mode of the studied compounds to tubulin.Alexander vonHumboldt FoundationAlexander von Humboldt FoundationV.B. is grateful for generous funding under the Georg Forster Research Fellowship received from the Alexander vonHumboldt Foundation. The authors acknowledge the technical assistance of Stephanie Kallis for the ZIKV antiviral assay, Natascha Stefan for the help in cell culture, and Heiko Rudy for the mass spectrometry data. M.R. thanks Torben LangHeinrich for his assistance in the synthesis of compound 9 a

MOLECULAR CONCEPTS OF MACROPHAGE TARGETING

Macrophages play an important role in the pathological development of different diseases. Therefore, macrophage targeting represents an important challenge in design of new medicines. This review gives a general presentation of small molecule-recognition concepts used for macrophage targeting. It describes mechanisms and systems for macrophage-targeted delivery, their obtaining and application