CoMFA Topomer, CoMFA, CoMSIA, HQSAR, docking molecular, dynamique study and ADMET study on phenyloxylpropyl isoxazole derivatives for coxsackie virus B3 virus inhibitors activity

Absent of drugs to treat entervirus infections, notably the coxsackievirus B3 virus (CVB3) which causes acute and chronic illnesses, the world remains in need of new antiviral drugs. The main objective of this work is the quantitative analysis of the structure-activity relationship (QSAR) of a series of phenyloxy propy isoxazoles derivatives against the CVB3 virus using two 2D approaches using the HQSAR method and 3D using the Topomer CoMFA and CoMFA and CoMSIA methods, followed by molecular docking analysis to validate established patterns and understand the mechanism of receptor-ligand interaction.  The results of the 2D / 3D QSAR models are quite satisfactory and give significant statistical results: R2 = 0.953, Q2 = 0.819, R2ext = 0.750 for the HQSAR, R2 = 0.980, Q2 = 0.83, R2 ext = 0.749 for the CoMFA topomer, R2 = 0.977, Q2 = 0.748, R2 ext = 0.843 for CoMFA, R2 = 0.962, Q2 = 0.804, R2 ext = 0.953 for CoMSIA.  It can be noted that these four models exceeded the external validation criteria used with success and respected the limits of the criteria of Tropsha and Glorbaikh. Based on the results obtained from the four models, we proposed a candidate for each model as an inhibitory agent against CVB3. Docking analyzes and molecular simulation were performed to understand the mechanism of interactions of these four designed compounds within the receptor active site. small-sized electron donor groups molecular docking shows that the proposed compounds performed greater interactions than the more active compound in the database. However, the groups added for the molecules A1, A2, A3, A4 help to create additional interactions between these ligands and the residues to stabilize the conformation of the ligands at the level of the binding pocket. The stability and binding modes of compounds A1, A2 and the most active compound in the data set were evaluated by molecular dynamics simulations during a simulation time of 100 ns. It is shown that the interactions of the selected compounds are stable and fluctuate weakly in the complex. Free energy calculations based on the MM-GBSA method confirmed that the two designed compounds A1 and A2 were able to form bonds in the protein cavity. In addition, the ADMET study and the five-parameter Lipinski's rule prediction were estimated to ensure that the proposed candidates are viable drugs with synthetic accessibility. These results can be used for the discovery of new drugs and can solve the problem of resistance of the CVB3 viru

An E9 multiplet of BPS states

We construct an infinite E9 multiplet of BPS states for 11D supergravity. For each positive real root of E9 we obtain a BPS solution of 11D supergravity, or of its exotic counterparts, depending on two non-compact transverse space variables. All these solutions are related by U-dualities realised via E9 Weyl transformations in the regular embedding of E9 in E10, E10 in E11. In this way we recover the basic BPS solutions, namely the KK-wave, the M2 brane, the M5 brane and the KK6-monopole, as well as other solutions admitting eight longitudinal space dimensions. A novel technique of combining Weyl reflexions with compensating transformations allows the construction of many new BPS solutions, each of which can be mapped to a solution of a dual effective action of gravity coupled to a certain higher rank tensor field. For real roots of E10 which are not roots of E9, we obtain additional BPS solutions transcending 11D supergravity (as exemplified by the lowest level solution corresponding to the M9 brane). The relation between the dual formulation and the one in terms of the original 11D supergravity fields has significance beyond the realm of BPS solutions. We establish the link with the Geroch group of general relativity, and explain how the E9 duality transformations generalize the standard Hodge dualities to an infinite set of `non-closing dualities'.Comment: 76 pages, 6 figure

Composición química parcial y actividad antimicrobiana de extractos de Daucus critinus Desf

The chemical composition of fatty acids and the unsaponifiable fraction of the roots, leaves and stems from Daucus crinitus Desf. were, determined using gas chromatography (GC) and gas chromatography-Mass Spectrometry (GC-MS). The fatty acid fractions of different organs (leaves, stems and roots) were characterized by lauric acid (17.9, 17.5 and 18.1 % respectively) and other long chain fatty acids (until C22). Qualitative and quantitative differences were reported between the unsaponifiable fractions of different organs from D. crinitus. The unsaponifiable fractions of the leaves, roots and stem showed high amounts of aliphatic components (83.4%, 87.2% and 91.4%, respectively). The monoterpen, diterpen and sesquiterpen components were only present in small percentages. The antimicrobial properties of the D. critinus extracts were tested on four different microorganisms. These extracts were found to be active against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Candida albicans.La composición química de los ácidos grasos y la fracción insaponificable de raíces, hojas, y tallos de Daucus crinitus Desf. fueron establecidas utilizando cromatografía de gases (GC) y cromatografía de gases-espectrometría de masas (GC-MS). La fracción de ácidos grasos de los diferentes órganos (hojas, tallos y raíces) se caracterizó por el ácido láurico (17.9, 17.5 y 18.1% respectivamente) y otros ácidos grasos de cadena larga (hasta C22). Diferencias cualitativas y cuantitativas se registraron entre las fracciones insaponificable de los diferentes órganos de D. crinitus. De hecho, las fracciones insaponificable de la raíz, de la hoja y del tallo mostraron cantidades altas de componentes alifáticos (83.4%, 87.2% y 91.4%, respectivamente). Los componentes monoterpénicos, diterpénicos y sesquiterpénicos solo estuvieron presentes en un pequeño porcentaje. Las propiedades antimicrobianas de los extractos de D. critinus fueron ensayadas en cuatro microorganismos diferentes. Estos extractos fueron activos contra Bacillus cereus, Staphylococcus aureus, Escherichia coli y Candida albicans

G2 Dualities in D=5 Supergravity and Black Strings

Five dimensional minimal supergravity dimensionally reduced on two commuting Killing directions gives rise to a G2 coset model. The symmetry group of the coset model can be used to generate new solutions by applying group transformations on a seed solution. We show that on a general solution the generators belonging to the Cartan and nilpotent subalgebras of G2 act as scaling and gauge transformations, respectively. The remaining generators of G2 form a sl(2,R)+sl(2,R) subalgebra that can be used to generate non-trivial charges. We use these generators to generalize the five dimensional Kerr string in a number of ways. In particular, we construct the spinning electric and spinning magnetic black strings of five dimensional minimal supergravity. We analyze physical properties of these black strings and study their thermodynamics. We also explore their relation to black rings.Comment: typos corrected (26 pages + appendices, 2 figures

Hidden Symmetries and Dirac Fermions

In this paper, two things are done. First, we analyze the compatibility of Dirac fermions with the hidden duality symmetries which appear in the toroidal compactification of gravitational theories down to three spacetime dimensions. We show that the Pauli couplings to the p-forms can be adjusted, for all simple (split) groups, so that the fermions transform in a representation of the maximal compact subgroup of the duality group G in three dimensions. Second, we investigate how the Dirac fermions fit in the conjectured hidden overextended symmetry G++. We show compatibility with this symmetry up to the same level as in the pure bosonic case. We also investigate the BKL behaviour of the Einstein-Dirac-p-form systems and provide a group theoretical interpretation of the Belinskii-Khalatnikov result that the Dirac field removes chaos.Comment: 30 page

Finite and infinite-dimensional symmetries of pure N=2 supergravity in D=4

We study the symmetries of pure N=2 supergravity in D=4. As is known, this theory reduced on one Killing vector is characterised by a non-linearly realised symmetry SU(2,1) which is a non-split real form of SL(3,C). We consider the BPS brane solutions of the theory preserving half of the supersymmetry and the action of SU(2,1) on them. Furthermore we provide evidence that the theory exhibits an underlying algebraic structure described by the Lorentzian Kac-Moody group SU(2,1)^{+++}. This evidence arises both from the correspondence between the bosonic space-time fields of N=2 supergravity in D=4 and a one-parameter sigma-model based on the hyperbolic group SU(2,1)^{++}, as well as from the fact that the structure of BPS brane solutions is neatly encoded in SU(2,1)^{+++}. As a nice by-product of our analysis, we obtain a regular embedding of the Kac-Moody algebra su(2,1)^{+++} in e_{11} based on brane physics.Comment: 70 pages, final version published in JHE

- Teucrium scorodonia L. tRNA-Leu (trnL) gene, partial sequence; trnL-trnF intergenic spacer, complete sequence; and trn-Phe (trnF) gene, partial sequence; chloroplast.

International audiencePublication de 27 séquences de Teucrium scorodonia - tRNA-Leu (trnL) gene, partial sequence; trnL-trnF intergenic spacer, complete sequence; and trn-Phe (trnF) gene, partial sequence; chloroplast