A PAMPA assay as fast predictive model of passive human skin permeability of new synthesized corticosteroid C-21 esters

The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate). The data were compared with parent corticosteroids with addition of mometasone furoate and hydrocortisone acetate. All newly synthesized corticosteroid C-21 esters have effective permeability coefficients higher then -6, mostly followed with high values of retention factors and low permeation. The examined compounds were grouped through relationship between obtained retention factors and permeation parameters (groups I-III). The classification confirmed group I (membrane retentions as well as permeation lower then 30%) for all corticosteroid standards except mometasone furoate, a potent topical corticosteroid which, with high membrane retention (81%) and low permeation (7.7%) fits into group III. The largest number of new synthesized corticosteroids C-21 esters, among them all fluocinolone acetonide C-21 esters, have high membrane retentions (32.4%-86.5%) and low permeations (1.3%-27.1%), fitting in group III. The classification was related to previously obtained anti-inflammatory activity data for the fluocinolone acetonide C-21 esters series. According to the PAMPA results the new synthesized esters could be considered as potential new prodrugs with useful benefit/risk ratio.     

Analysis of the essential oil of Teucrium polium ssp. capitatum from the Balkan Peninsula

The chemical composition of the essential oil of the aerial parts of Teucrium polium ssp. capitatum collected during the flowering period from rocky places and dry pastures, (Serbia, Nis, Kamenica), and dunes along the sea-side, (Bulgaria, Burgas, Primorsko) has been studied by GC and GC/MS. The identified compounds, 45 for the oil from Serbia and 44 for that from Bulgaria, amounted to 97.3% and 96.4% of the oils, respectively. The dominant constituents of the Serbian oil were sesquiterpenes {59.6%, the most abundant components being germacrene D (31.8%), trans-caryophyllene (8.8%) and bicyclogermacrene (6.2%)}, while monoterpenes accounted for 37.5% {the most abundant components being linalool (14.0%) and beta-pinene (10.7%)}. The essential oil from Bulgaria was characterized by a high percentage of monoterpenes, amounting to 62.9% {the most abundant components being beta-pinene (26.8%), alpha-pinene (9.3%) and limonene (6.4%)}, while sesquiterpenes accounted for 33.5% (the most abundant component was germacrene D 17.7%)}.     

Synthesis, characterization and antiproliferative activity of transition metal complexes with 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanoic acid (oxaprozin)

A series of novel Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes with oxaprozin (Hoxa), a non-steroidal anti-inflammatory drug, has been synthesized. The drug and complexes have been characterized by elemental and thermogravimetric (TG) analysis, Fourier transform (FT)-IR, 1H-NMR, 13C-NMR, UV-Vis spectroscopy and magnetic susceptibility measurements. The (pseudo)octahedral geometry has been proposed for all complexes based on electronic spectra and magnetic moments. With exception of the Cu(II) complex, where bridging bidentate mode of COO groups has been found, FT-IR spectra confirmed chelately coordinated COO groups in the other complexes. The general formula of the complexes is [M(H2O)2(oxa)2 ·χH2O, with χ=2 for M=Mn, Co and Ni and χ=1.5 for Zn. The binuclear Cu(II) complex, [Cu2(H2O)2(OH)(oxa)3]·2H2O, has strong Cu-Cu interactions of antiferromagnetic type. The complexes and Hoxa did not exhibit the cytotoxic effect to peritoneal macrophages. For the first time these complexes have been tested for their in vitro antiproliferative activity against human colon and breast cancer cell lines, HCT-116 and MDA-231, respectively. For all investigated compounds significant antiproliferative effects have been observed. Ni(II) complex has been shown to be a promising antiproliferative agent exerting excellent activity against HCT-116 even in nanomolar concentrations.     

Linkless and Flat Embeddings in 3-Space

We consider piecewise linear embeddings of graphs in 3-space ℝ³. Such an embedding is linkless if every pair of disjoint cycles forms a trivial link (in the sense of knot theory). Robertson, Seymour and Thomas (J. Comb. Theory, Ser. B 64:185–227, 1995) showed that a graph has a linkless embedding in ℝ³ if and only if it does not contain as a minor any of seven graphs in Petersen’s family (graphs obtained from K ₆ by a series of YΔ and ΔY operations). They also showed that a graph is linklessly embeddable in ℝ³ if and only if it admits a flat embedding into ℝ³, i.e. an embedding such that for every cycle C of G there exists a closed 2-disk D⊆ℝ³ with D∩G=∂D=C. Clearly, every flat embedding is linkless, but the converse is not true. We consider the following algorithmic problem associated with embeddings in ℝ³:     

Crystallographic evidence of nitrate-pi interactions involving the electron-deficient 1,3,5-triazine ring

The reaction of Zn(NO3)2.6H2O or Cu(NO3)2.3H2O with the star-shaped ligand 2,4,6-tris(di-2-picolylamino)[1,3,5]triazine (dipicatriz) in acetonitrile results in the formation of the mono- or trinuclear coordination compounds [Zn(dipicatriz)(NO3)2] (1), [Zn3(dipicatriz)(NO3)6](CH3CN)3 (2), and [Cu3(dipicatriz)(NO3)2(H2O)6](NO3)4 (3), depending on the metal-to-ligand ratios used during the crystallization process. Their crystal structures exhibit unique supramolecular interactions. Compounds 1 and 2 show anion-pi interactions between coordinated nitrate ions and the s-triazine ring. Compound 3 exhibits remarkable interactions between two noncoordinated nitrate anions and the two faces of the electron-deficient heteroaromatic ring, corroborating earlier theoretical investigations in this area. New theoretical investigations have been carried out on nitrate-pi interactions, taking into account the particular position of the anion toward the aromatic ring observed in the crystal structures.     

1-Butanol + hexylamine + n-heptane at temperature range (288.15–323.15 K): Experimental density data,excess molar volumes determination and modeling with cubic EOS

Densities ρ of the ternary system 1-butanol + hexylamine + n-heptane and binaries: 1-butanol + hexylamine and hexylamine + n-heptane within the temperature range (288.15–323.15 K) and atmospheric pressure are reported. Excess molar volumes V^E were calculated from the density data and fitted by the Redlich–Kister and Nagata and Tamura equations. The results are analyzed in terms of the molecular interactions between the components of mixtures.     

Reflexivity defect of spaces of linear operators

For a finite-dimensional linear subspace S⊆L(V,W) and a positive integer k, the k-reflexivity defect of S is defined by rd_k(S)=dim(Ref_k(S)/S), where Ref_k(S) is the k-reflexive closure of S. We study this quantity for two-dimensional spaces of operators and for single generated algebras and their commutants.     

Radiological,structural and chemical characterization of raw materials and ceramic tiles in Serbia

Journal of Radioanalytical and Nuclear Chemistry - This paper presents the results of the gamma spectrometric analysis of 27 raw materials used for the production of ceramic tiles in Serbia and 9...