RESUMEN

Bocconia arborea S. Watson (Papaveraceae) is an abundant medicinal plant in the North of Morelos State, Mexico, which is used for the treatment of several diseases. The aim of current investigation was to isolate the compounds responsible of the relaxant effect shown by the active extracts. Thus, phytochemical bio-guided fractionation allowed the isolation of angoline (1), dihydrosanguinarine (2), bocconarborine A (3), oxisanguinarine (4), and oxychelerithrine (5) from dichloromethanic and methanolic extracts from the bark of Bocconia arborea (Papaveraceae). The relaxant study on aortic and tracheal rat rings of all benzophenanthridines indicates that 1 was the most active compound of the entire series investigated. Angoline (1) induces its relaxant effect by a concentration-dependent manner through the calcium channel blockade in both tissues.

RESUMEN

In the title compounds, 3-(dihydroxyboryl)anilinium bisulfate monohydrate, C6H9BNO2+·HSO4-·H2O (I), and 3-(dihydroxyboryl)anilinium methyl sulfate, C6H9BNO2+·CH3SO4- (II), the almost planar boronic acid molecules are linked by pairs of O-H...O hydrogen bonds, forming centrosymmetric motifs that can be described by the graph-set R22(8) motif. In both crystals, the B(OH)2 group acquires a syn-anti conformation (with respect to the H atoms). The presence of the hydrogen-bonding functional groups B(OH)2, NH3+, HSO4-, CH3SO4- and H2O generates three-dimensional hydrogen-bonded networks, in which the bisulfate (HSO4-) and methyl sulfate (CH3SO4-) counter-ions act as the central building blocks within the crystal structures. Furthermore, in both structures, the packing is stabilized by weak boron-π interactions, as shown by noncovalent interactions (NCI) index calculations.

RESUMEN

As the rate of discovery of new antibacterial compounds for multidrug-resistant bacteria is declining, there is an urge for the search for molecules that could revert this tendency. Acinetobacter baumannii has emerged as a highly virulent Gram-negative bacterium that has acquired multiple resistance mechanisms against antibiotics and is considered of critical priority. In this work, we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against A. baumannii. QSPR mathematical validation (R2 = 70.27, RN = -0.008, a(R2) = 0.014, and δK = 0.021) and its prediction ability (Q2LMO= 67.89, Q2EXT = 67.75, a(Q2) = -0.068, δQ = 0.0, rm2¯ = 0.229, and Δrm2 = 0.522) were obtained with different statistical parameters; additional validation was done using three sets of external molecules (R2 = 72.89, 71.64 and 71.56). We used the QSPR model to perform a virtual screening on the BIOFACQUIM natural product database. From this screening, our model showed that molecules 32 to 35 and 54 to 68, isolated from different extracts of plants of the Ipomoea sp., are potential antibacterials against A. baumannii. Furthermore, biological assays showed that molecules 56 and 60 to 64 have a wide antibacterial activity against clinically isolated strains of A. baumannii, as well as other multidrug-resistant bacteria, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Finally, we propose 60 as a potential lead compound due to its broad-spectrum activity and its structural simplicity. Therefore, our QSPR model can be used as a tool for the investigation and search for new antibacterial compounds against A. baumannii.

RESUMEN

In the title crystal, the salt [CsMe2P(S)NP(S)Me2] is self-assembled as an undulating supra-molecular two-dimensional polymeric structure, poly[(µ4-tetra-methyl-dithio-imidodiphosphinato)caesium], [Cs(C4H12NP2S2)] n , which is parallel to the bc plane. The Cs cations are hexa-coordinated, being chelated by two thio-imidophosphinate groups and two sulfur atoms from neighboring ligands. The anions are linked to the Cs cations by Cs⋯S and Cs⋯N electrostatic inter-actions.

RESUMEN

The synthesis and characterization of two new 1,3,5-triazines containing 2-(aminomethyl)-1H-benzimidazole hydrochloride as a substituent are reported, namely, 2-{[(4,6-dichloro-1,3,5-triazin-2-yl)amino]methyl}-1H-benzimidazol-3-ium chloride, C11H9Cl2N6+·Cl- (1), and bis(2,2'-{[(6-chloro-1,3,5-triazine-2,4-diyl)bis(azanediyl)]bis(methylene)}bis(1H-benzimidazol-3-ium)) tetrachloride heptahydrate, 2C19H18ClN92+·4Cl-·7H2O (2). Both salts were characterized using single-crystal X-ray diffraction analysis and IR spectroscopy. Moreover, the NMR (1H and 13C) spectra of 1 were obtained. Salts 1 and 2 have triclinic symmetry (space group P\overline{1}) and their supramolecular structures are stabilized by hydrogen bonding and offset π-π interactions. In hydrated salt 2, the noncovalent interactions yield pseudo-nanotubes filled with chloride anions and water molecules, which were modelled in the refinement with substitutional and positional disorder.

RESUMEN

In this work the interaction of halide anions and simple aromatic compounds with a bichromophoric fluorescent dyad derived from 1,8-naphthalimide (NAPIM) and 5-(dimethylamino)naphthalene-1-sulfonyl (DANS) was studied using electronic spectroscopy, 1H, and 19F NMR spectroscopy and quantum chemistry modeling (b3lyp/def2-TZVP). The NAPIM-DANS dyad interacts with electron-rich guests with binding constants in the range of 6×103 to 8×103M-1 in CHCl3. The formed complexes are stabilized through aryl C-H … anion and aryl C-H … π interactions.

RESUMEN

In this study, we synthesized five N-Boc-L-tyrosine-based analogues to glitazars. The in vitro effects of compounds 1-5 on protein tyrosine phosphatase 1B (PTP-1B), peroxisome proliferator-activated receptor alpha and gamma (PPARα/γ), glucose transporter type-4 (GLUT-4) and fatty acid transport protein-1 (FATP-1) activation are reported in this paper. Compounds 1 and 3 were the most active in the in vitro PTP-1B inhibition assay, showing IC50s of approximately 44 µM. Treatment of adipocytes with compound 1 increased the mRNA expression of PPARγ and GLUT-4 by 8- and 3-fold, respectively. Moreover, both compounds (1 and 3) also increased the relative mRNA expression of PPARα (by 8-fold) and FATP-1 (by 15-fold). Molecular docking studies were performed in order to elucidate the polypharmacological binding mode of the most active compounds on these targets. Finally, a murine model of hyperglycemia was used to evaluate the in vivo effectiveness of compounds 1 and 3. We found that both compounds are orally active using an exploratory dose of 100 mg/kg, decreasing the blood glucose concentration in an oral glucose tolerance test and a non-insulin-dependent diabetes mellitus murine model. In conclusion, we demonstrated that both molecules showed strong in vitro and in vivo effects and can be considered polypharmacological antidiabetic candidates.

Asunto(s)

RESUMEN

Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides 1-8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1-8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1-8 were carried out through reaction of 5(6)-nitro-1H-benzimidazol-2-amine (12) with 2-chlroactemides 10a-h, in the presence of K2CO3 and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardiaintestinalis and Entamoebahistolytica) and a urogenital tract parasite (Trichomonasvaginalis) were tested. Compound 7 showed an IC50 of 3.95 µM and was 7 time more active against G.intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T.vaginalis compared with benznidazole.

Asunto(s)

RESUMEN

The cation of the title solvated salt, C42H42N2P2 (2+)·2Br(-)·2CH2Cl2, lies on a crystallographic twofold rotation axis. The 1,2-di-amino-cyclo-hexane fragment has a chair conformation with two N atoms in a transoid conformation [N-C-C-N = 163.4 (2)°]. In the crystal, the cations are linked to the anions by N-H⋯Br and C-H⋯Br hydrogen bonds, forming a chain structure along the c axis. The di-chloro-methane mol-ecule takes part in the hydrogen-bond network through C-H⋯π and C-H⋯Br inter-actions.

RESUMEN

In the title compound, C33H38N2O2, each of the cyclo-hexyl rings adopts a chair conformation. The two planes involving carbonyl groups, C-(C=O)-N and N-(C=O)-N, are oriented at a dihedral angle of 62.28 (10)°. In the crystal, two neighboring mol-ecules are linked by a pair of N-H⋯O inter-actions, generating an inversion dimer. The dimers are inter-connected by C-H⋯O hydrogen bonds into a supra-molecular chain along the a-axis direction.

RESUMEN

In the title compound, C28H22OP2, each of the P atoms has an almost perfect pyramidal geometry, with C-P-C angles varying from 100.63 (10) to 102.65 (9)°. In the crystal, neighbouring mol-ecules are linked via weak C-H⋯π inter-actions, forming supra-molecular chains along the b-axis direction.

RESUMEN

The whole mol-ecule of the title compound, C17H10N4O5·2H2O, is generated by twofold rotation symmetry and it crystallized as a dihydrate. The planes of the phthalimide moieties and the urea unit are almost normal to one another, with a dihedral angle of 78.62 (9)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional framework structure. The crystal packing also features C-H⋯O hydrogen bonds and slipped parallel π-π inter-actions [centroid-centroid distance = 3.6746 (15) Å] involving the benzene rings of neighbouring phthalimide moieties.

RESUMEN

A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10 µM), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11ß-HSD1. In this model, compound 1 binds into the catalytic site of 11ß-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+).

Asunto(s)

RESUMEN

In the title salt, C23H21NOP(+)·Br(-), the dihedral angles between the phenyl rings are 70.41 (18), 73.6 (2) and 80.85 (19)°. In the crystal, neighboring mol-ecules are linked through an N-H⋯Br hydrogen bond and four weak C-H⋯Br contacts, forming a three-dimensional network.

RESUMEN

In the title compound, C12H15NO4, the dihedral angle between the acetamide group and the ring is 29.6 (2)(su?)°. In the crystal mol-ecules are linked through N-H⋯O and O-H⋯O hydrogen bonds, thereby forming corrugated sheets propagating in the ac plane. These sheets are composed of R4(4)(28) graph-set motifs.

RESUMEN

The asymmetric unit of the title compound, C(11)H(16)N(2)O(2), contains two independent conformational isomers which show intra-molecular aromatic-imine O-H⋯N hydrogen bonds. In the crystal, neighboring mol-ecules are linked through inter-molecular aliphatic-aliphatic O-H⋯N, aliphatic-aromatic N-H⋯O and C-H⋯O inter-actions into hydrogen-bonded layers parallel to the ab plane.

RESUMEN

In the presence of water, benzene-1,4-diboronic acid (1,4-bdba) and 4,4'-bipyridine (4,4'-bpy) form a cocrystal of composition (1,4-bdba)(4,4'-bpy)(2)(H(2)O)(2), in which the molecular components are organized in two, so far unknown, cyclophane-type hydrogen-bonding patterns. The asymmetric unit of the title compound, C(6)H(8)B(2)O(4).2C(10)H(8)N(2).2H(2)O, contains two 4,4'-bpy, two water molecules and two halves of 1,4-bdba molecules arranged around crystallographic inversion centers. The occurrence of O-H...O and O-H...N hydrogen bonds involving the water molecules and all O atoms of boronic acid gives rise to a two-dimensional hydrogen-bonded layer structure that develops parallel to the (01-4) plane. This supramolecular organization is reinforced by pi-pi interactions between symmetry-related 4,4'-bpy molecules.

RESUMEN

In the title compound, 2C(6)H(9)BNO(2) (+)·SO(4) (2-), the dihydroxy-boryl group of one of the two independent boronic acid mol-ecules participates in (B)O-H⋯O(B) and N-H⋯O(B) hydrogen bonds, while the second is involved mainly in the formation of the charge-assisted heterodimeric synthon -B(OH)(2)⋯(-)O(2)SO(2) (-). These aggregates are further connected through N-H⋯O(sulfate) inter-actions, forming a complex three-dimensional hydrogen-bonded network.

RESUMEN

In the title compound, C(6)H(8)BNO(2)·H(2)O, the almost planar boronic acid mol-ecules (r.m.s. deviation = 0.044 Å) form inversion dimers, linked by pairs of O-H⋯O hydrogen bonds. The water mol-ecules link these dimers into [100] chains by way of O-H⋯O hydrogen bonds, and N-H⋯O links generate (100) sheets.

RESUMEN

The [4.3.0]heterobicyclic title structure, C(19)H(14)BNO(3), is composed of a five-membered OBNC(2) ring and a six-membered OBNC(3) ring, each of which has an approximate envelope conformation. The coordination geometry of the B atom is distorted tetra-hedral. In the crystal structure, centrosymmetrically related mol-ecules are associated through pairs of O-H⋯O hydrogen bonds.