Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI$_{50}$ ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα

A new group of compounds derived from 4-, 5-, 6- and 7-aminoindoles with antimicrobial activity

Antimicrobial activity of the substituted amides and pyrroloquinolines on the basis of 4-, 5-, 6-, 7-aminoindoles was etermined in our study, as well as the spectra of their action against Gram-positive and Gram-negative microorganisms, which are causative agents of non-specific and certain specific human infectious diseases. Moreover, we evaluated the synthetic potentials of the substituted 4-, 5-, 6-, 7-aminoindoles as the starting compounds for synthesizing a series of indolylamides and pyrroloquinolines. Also, the prospects for targeted synthesis of biologically active compounds based on indole-type aromatic amines were determine

Synthesis and in vitro biological evaluation of 2,3-substituted quinoline derivatives

Thesis (MSc)--Rhodes University, Science Faculty, Department of Chemistry, 202

Ingeniería de una lacasa fúngica como biocatalizador para síntesis orgánica

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Genética, Fisiología y Microbiología, leída el 06-03-2020Laccases (EC 1.10.3.2) are multicopper oxidases with the capability to oxidize a great variety of aromatic compounds and some metals. Their substrate versatility and their low catalytic requirements turn these enzymes into biocatalysts of interest for different sectors. One of the most promising applications of laccases is the synthesis of high value organic compounds, providing higher selectivity than chemical reactions and generating less toxic residues. For many of these reactions fungal high redox potential laccases are required due to their higher oxidation capabilities. One of these reactions is the synthesis of polyaniline (PANI), an electroconductive polymer with a large number of applications. However, the reaction conditions (acid pH and surfactants presence) and the high redox potential of aniline at acid pH hinder laccase activity, requiring the engineering of the enzyme to optimize their activity and stability under these conditions. In previous works, two high redox potential fungal laccases were evolved in the laboratory for their expression in Saccharomyces cerevisiae. These enzymes were thereafter recombined to obtain a library of chimeric laccases with different activities and stabilities. Among them, 7D5 laccase was selected as starting point for this Doctoral Thesis...Las lacasas (EC 1.10.3.2) son oxidasas multicobre capaces de oxidar una gran variedad de compuestos aromáticos y ciertos metales. Su versatilidad de sustrato y sus bajos requerimientos catalíticos hacen de estas enzimas biocatalizadores de interés para distintos sectores. Una de las aplicaciones más interesantes de las lacasas es la síntesis de compuestos orgánicos de alto valor añadido, ofreciendo una mayor selectividad que las reacciones químicas y con menor generación de residuos tóxicos. Para muchas de estas reacciones, se requiere el empleo de lacasas fúngicas de alto potencial redox debido a su mayor poder oxidativo. Tal es el caso de la polimerización de anilina para obtener polianilina (PANI), un polímero electroconductor con una amplia variedad de aplicaciones. Sin embargo, las condiciones de reacción (pH ácido y presencia de surfactantes) y el alto potencial redox de la anilina a pH ácido dificultan la acción de la enzima, haciendo necesaria su ingeniería para optimizar su actividad y estabilidad en dichas condiciones. En estudios previos, dos lacasas fúngicas de alto potencial redox fueron evolucionadas en el laboratorio para su expresión en Saccharomyces cerevisiae. Posteriormente, se recombinaron dichas enzimas para obtener una librería de lacasas quiméricas con diferentes actividades y estabilidades. De entre ellas, se seleccionó la lacasa 7D5 como punto de partida de esta Tesis Doctoral...Fac. de Ciencias BiológicasTRUEunpu

Pain Management

Pain Management - Current Issues and Opinions is written by international experts who cover a number of topics about current pain management problems, and gives the reader a glimpse into the future of pain treatment. Several chapters report original research, while others summarize clinical information with specific treatment options. The international mix of authors reflects the "casting of a broad net" to recruit authors on the cutting edge of their area of interest. Pain Management - Current Issues and Opinions is a must read for the up-to-date pain clinician