Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors.     

Spatial arrangement of the structural elements ofvocal fold layers: An adjustment to the vibration process

It is well established that the multilayered structure of the vocal fold is highly adjusted to the requirements of the vibration process during phonation. There is also some partial data indicating that the spatial arrangement of each vocal fold layer corresponds to the functional requirements, and thus facilitate the phonation process. Nevertheless, all reports on the spatial arrangement of the vocal fold structures deal only with an individual element of the vocal fold histologic structure. The present study encompasses the spatial histologic analysis of all major elements of the vocal fold layers. It was demonstrated that the vocal fold epithelial cells, the connective and muscle fibers, and even the blood vessels run parallel to the vocal fold free edge, which indicates a high adjustment to the phonation requirements and the vibration process.     

Weak continuity in convection problems

Basic aspects of steady natural convection in fluid-saturated porous media are studied, such as the existence of weak solutions, some regularity properties, a minimax principle and the determination of a sufficient condition for uniqueness, which is very unlikely to happen if the Rayleigh number is not less than a critical value.     

New Spectroscopic Information on 98Pd

Neutron deficient ⁹⁸Pd nuclei were produced in the ⁵⁰Cr(⁵⁸Ni,2p2α)⁹⁸Pd reaction at a beam energy of 261 MeV. A revision and extension of the level structure of ⁹⁸Pd is proposed. About 40 new transitions have been assigned to, and placed in the level scheme of this nucleus. A sequence of states are candidates for the negative parity 4—quasiparticle states built on the πg _9/2 ^?3 πp _1/2 ^?1 configuration predicted in the framework of the nuclear shell model.     

Structure and reactivity of vanadium-phosphorus oxides

The contribution of thermal methods of analysis to the study of the structure and reactivity of vanadium-phosphorus oxides is examined. In particular, data are reported on the solid-state reaction VOHPO₄·1/2H₂O(VO)₂P₂O₇+2 H₂O for VOHPO₄·1/2H₂O prepared in different ways, on the redox properties of oxidation and reduction of vanadium for catalysts prepared with different PV atomic ratios in the range 0.9–1.3, and on the surface properties determined by TPD of catalysts with different PV ratios. The relationship between these properties and the catalytic properties in the selective oxidation ofn-butane and but-1-ene is discussed.

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Zusammenfassung Der Beitrag thermischer Analysenmethoden zur Untersuchung der Struktur und Reaktivität von Vanadin-Phosphor-Oxiden wird erörtert. Insbesondere werden sich auf die Festkörperreaktion 2VOHPO₄.1/2H₂O(VO)₂P₂O₇+2H₂O für auf verschiedene Weise dargestelltes VOHPO₄.1/2H₂O, auf die Redox-Eigenschaften von Vanadin in Katalysatoren mit P/V-Atomverhältnissen im Bereich 0.9–1.3 und auf durch TPD bestimmte Oberflächeneigenschaften von Katalysatoren mit unterschiedlichen P/V-Verhältnissen beziehende Angaben gemacht. Zusammenhänge zwischen diesen Eigenschaften und den katalytischen Eigenschaften bei der selektiven Oxydation von n-Butan und N-Buten werden diskutiert.

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- . , VOHPO₄ · 1/2H₂O, VOHPO₄ · 1/2H₂O(VO)₂P₂O₇ + 2H₂O, - PV 0,91,3. - 1-.

     

Characterization of the bis(β-diimino-tetracyano-pyrrolizinido)-metal(II) complexes incorporated in polymeric matrices

The bis(-diimino-tetracyano-pyrrolizinido)-Cu(II) complex (CuL₂) has been incorporated in polystyrene (0.28% w/w), by evaporating tetrahydrofuran solutions either at room temperature (a) or at 100°C (b). From IR and UV-vis measurements and optical microscopy on the resulting films (a orb, thickness 50 m) it is concluded that CuL₂ is present as a concentrated (C10^–1 M) THF solution ina and as small solid particles (diameter <1 m) inb. The difference in colour of the films (dark bluea, light blueb), due to the different physical state of CuL₂ in the matrix, is expected, and has been preliminarily shown using similar films based on NiL₂, to be useful for sensing organic vapours in the atmosphere.     

Non-linear protocell models: synchronization and chaos

We consider generic protocells models allowing linear and non-linear kinetics for the main involved chemical reactions. We are interested in understanding if and how the protocell division and the metabolism do synchronise to give rise to sustainable evolution of the protocell.