NMR analysis, cytotoxic activity and theoretical study of a complex between SRPIN340 and p-sulfonic acid calix[6]arene.

Aim: This study aimed to enhance the aqueous dissolution of SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). Materials & Methods: A complex with p-sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via 1H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines. Results & conclusion: The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by 1H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.

[Box: see text].

Insights on physicochemical aspects of chitosan dispersion in aqueous solutions of acetic, glycolic, propionic or lactic acid.

Chitosan is a polysaccharide well-known for its applicability as a biocompatible, biodegradable, and non-toxic material to produce drugs excipients and food coatings. Acidic media are required to disperse chitosan, and aqueous solutions of acetic acid have been typically used for this purpose. However, this acid has several sensory drawbacks. In this study, chitosan was dispersed [0.1 g·(100 mL)-1] in aqueous media containing acetic (AA), glycolic (GA), propionic (PA), or lactic (LA) acid, at 10, 20, 30, 40, or 50 mmol·L-1. The increase of acid concentration reduced pH and viscosity of the dispersions, and |ζ potential| of dispersed particles. Conversely, it increased electrical conductivity and density of the dispersions, and hydrodynamic diameter of dispersed particles. At a given concentration, these effects were slightly more pronounced for dispersions formed with GA or LA, compared to AA or PA. FT-IR data suggested more intense attractive interactions of chitosan chains with glycolate and lactate anions, than with acetate and propionate. Chitosan chains interacted more strongly with hydroxylated acids counter-anions than with their non-hydroxylated counterparts, leading to slight quantitative changes of physicochemical properties of these systems. Then, in physicochemical terms, GA, LA or PA are suitable to replace AA when preparing aqueous chitosan dispersions for technological applications.

Semisynthetic Phenol Derivatives Obtained from Natural Phenols: Antimicrobial Activity and Molecular Properties.

Semisynthetic phenol derivatives were obtained from the natural phenols: thymol, carvacrol, eugenol, and guaiacol through catalytic oxychlorination, Williamson synthesis, and aromatic Claisen rearrangement. The compounds characterization was carried out by 1H NMR, 13C NMR, and mass spectrometry. The natural phenols and their semisynthetic derivatives were tested for their antimicrobial activity against the bacteria: Staphylococcus aureus, Escherichia coli, Listeria innocua, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, Salmonella enterica ssp. enterica, and Bacillus cereus. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were determined using concentrations from 220 to 3.44 µg mL-1. Most of the tested compounds presented MIC values ≤220 µg mL-1 for all the bacteria used in the assays. The molecular properties of the compounds were computed with the PM6 method. Through principle components analysis, the natural phenols and their semisynthetic derivatives with higher antimicrobial potential were grouped.

Structural elucidation of dioxa-cage compounds from tetrahydroisobenzofuran-1(3H)-one: analysis of NMR data and GIAO chemical shifts calculations.

The polycyclic compounds, especially the dioxa-cages, have attracted considerable attention in recent years. In our work, a series of 9ß-substituted 3-oxo-4,11-dioxatetracyclo[5.2.1.15,8 .02,6 ]undecane compounds were unexpectedly isolated during bromination, chlorination and epoxidation reactions of the 3-hydroxy-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one. After careful analysis of the NMR data, the chemical shifts of the isolated and the expected products were predicted by theoretical calculations using density functional theory and gauge including atomic orbitals. The best correlation between calculated and experimental data was evaluated by comparing mean absolute errors and applying DP4 probability methodology. Results from both approaches indicated a correct structural elucidation. Copyright © 2016 John Wiley & Sons, Ltd.

Induction of G2/M arrest, caspase activation and apoptosis by α-santonin derivatives in HL-60 cells.

Sesquiterpene lactones (SLs) are natural products with a variety of biological activities. Previously, we demonstrated the cytotoxic effects of three new α-santonin derivatives on different tumor cell lines with low toxic effects upon peripheral human leukocytes. Here, we evaluated the mechanism of action triggered by these derivatives. HL-60 cell cycle determined after 24h treatment revealed a significant inhibition on cell-cycle progression and leading to an increasing of cells in G2/M [7.6% and 9.0% for compound 3% and 9.0% and 8.6% for compound 4 (1 and 2 µM, respectively)]. However, after 48 h exposure, all compounds caused G2/M reduction and a significant DNA fragmentation. Compounds 2, 3 and 4 were able to induce apoptosis on leukemia cells, which was corroborated by phosphatidyserine externalization and activation of caspases-3 and -7 after 24h exposure. None of the derivatives analyzed caused depolarization of mitochondrial membrane within 24h of incubation, suggesting the involvement of the extrinsic apoptotic pathway in the death process. The antiproliferative action of these compounds is related to the DNA synthesis inhibition and cell cycle arrest, which probably lead to apoptosis activation. Therefore, these santonin derivatives are promising lead candidates for development of new cytotoxic agents.

Chemical characterization of volatile compounds of Lantana camara L. and L. radula Sw. and their antifungal activity.

A comparative study of the chemical composition of essential oils of two very similar species of the Verbenaceae family (Lantana camara and L. radula) revealed that the main components of essential oil of L. camara were germacrene-D (19.8%) and E-caryophyllene (19.7%), while those of L. radula were E-caryophyllene (25.3%), phytol (29.2%) and E-nerolidol (19.0%). We have hypothesized that the observed differences could contribute to the differentiated reaction of the two species of Lantana to the attack of the phytopathogenic fungi Corynespora cassiicola. An experiment, involving C. cassiicola cultivation in culture media containing volatile oils of the two species demonstrated that the oils of L. radula were more fungistatic than the oils of L. camara, in accordance with the in vivo observations. It is likely that E-nerolidol and phytol, only found in the oil of L. radula, play a significant role in the effects of L. radula on C. cassiicola.

Effect of Magnesium phosphoricum 12c on Sodium Dodecylsulphate by 13C nuclear magnetic resonance / Efeito do Magnesium phosphoricum 12c em Dodecilsulfato de sódio mediante ressonância magnética nuclear C13

Sodium dodecylsulphate (SDS) dissolved in water forms aggregates whose thermodynamic properties are well defined. The interest in polymer-surfactant systems derives from increasing possibilities to apply them in pharmaceutics, cosmetics and environmental protection. Nutrient content of soils after many years of use is a concern in many areas; on the other hand, the metabolism of plants approaches equilibrium when the conditions necessary for their growth are present. Magnesium and phosphorus are important nutrients for plants and high dilutions of Magnesium phosphoricum (Mag-p) may carry information related to them. Aims: To study the influence of Mag-p on SDS aggregates. Methods: the effect of Mag-p dilution 12c on the structure of SDS aggregates was assayed through 13C nuclear magnetic resonance. Results: The spectrum of SDS and Mag-p 12c in D2O presented an extra signal in 221.41 ppm when compared to the SDS / D2O spectrum. The C=O group of ketones and aldehydes absorb around 200 ppm. The carbon carbonyl shows large spin-lattice relaxation times (T1) and weak NOE (Nuclear Overhauser Effect) enhancement, thus signal from this type of atom are very weak when compared to signals from carbon atoms with hydrogen. The signal present in 221.41 ppm was comparable in size to the other signals in the spectrum indicating that it was not a machine-generated artifact. The experiments carried out in this work suggest that this signal was induced by a combination of SDS and the high diluted solution.

Dodecilsulfato de Sódio (SDS) dissolvido em água forma agregados cujas propriedades termodinâmicas são conhecidas. O interesse no estudo de sistemas polímero-surfactantes decorre das potenciais aplicações destes nas áreas de farmácia, cosmética e proteção ambiental. A quantidade de nutrientes no solo, após muitos anos de uso é um tema importante para muitas áreas; por outro lado, o metabolismo das plantas tendem ao equilíbrio quando as condições necessárias para o crescimento estão presentes. Magnésio e Fósforo são nutrientes importantes para plantas e altas diluições de Magnesium phosphoricum (Mag-p) potencialmente contém informações importantes sobre estas substâncias. Objetivos: estudar a influência de Mag-p em agragados de SDS. Métodos: o efeito da diluição 12c de Mag-p sobre a estrutura de agregados de SDS foi estudada através de ressonância magnética nuclear de 13C. Resultados: O espectro de SDS e Mag-p 12c em D2O apresentou um sinal extra em 221.41 ppm, quando comparado com o espectro de SDS / D2O. O grupamento C=O group das cetonas e aldeídos absorvem por volta de 200 ppm. O Carbono da carbonila mostrou um aumento no tempo de relaxação spin-rede (T1) e fraco aumento NOE (Nuclear Overhauser Effect), uma vez que este tipo de átomo geram sinais fracos em relação aos carbonos ligados a hidrogênios. O sinal presente em 221.41 ppm foi comparável em tamanho a outros sinais do espectro, sugerindo que este sinal pode não ser devido a um arfetato experimental. Os resultados obtidos sugerem que este sinal foi pode ter sido originado pela combinação de SDS com as moléculas da alta diluição.

Effect of Magnesium phosphoricum 12c on Sodium Dodecylsulphate by 13C Nuclear Magnetic Resonance / Efeito do Magnesium phosphoricum 12c em Dodecilsulfato de sódio mediante ressonância magnética nuclear C13

Sodium dodecylsulphate (SDS) dissolved in water forms aggregates whose thermodynamic properties are well defined. The interest in polymer-surfactant systems derives from increasing possibilities to apply them in pharmaceutics, cosmetics and environmental protection. Nutrient content of soils after many years of use is a concern in many areas; on the other hand, the metabolism of plants approaches equilibrium when the conditions necessary for their growth are present. Magnesium and phosphorus are important nutrients for plants and high dilutions of Magnesium phosphoricum (Mag-p) may carry information related to them. Aims: To study the influence of Mag-p on SDS aggregates. Methods: the effect of Mag-p dilution 12c on the structure of SDS aggregates was assayed through 13C nuclear magnetic resonance. Results: The spectrum of SDS and Mag-p 12c in D2O presented an extra signal in 221.41 ppm when compared to the SDS / D2O spectrum. The C=O group of ketones and aldehydes absorb around 200 ppm. The carbon carbonyl shows large spin-lattice relaxation times (T1) and weak NOE (Nuclear Overhauser Effect) enhancement, thus signal from this type of atom are very weak when compared to signals from carbon atoms with hydrogen. The signal present in 221.41 ppm was comparable in size to the other signals in the spectrum indicating that it was not a machine-generated artifact. The experiments carried out in this work suggest that this signal was induced by a combination of SDS and the high diluted solution.(AU)

Dodecilsulfato de Sódio (SDS) dissolvido em água forma agragados cujas propriedades termodinâmicas são conhecidas. O interesse no estudo de sistemas polímero-surfactantes decorre das potenciais aplicações destes nas áreas de farmácia, cosmética e proteção ambiental. A quantidade de nutrientes no solo, após muitos anos de uso é um tema importante para muitas áreas; por outro lado, o metabolismo das plantas tendem ao equilíbrio quando as condições necessárias para o crescimento estão presentes. Magnesio e Fósforo são nutrientes importantes para plantas e altas diluições de Magnesium phosphoricum (Mag-p) potencialmente contém informações importantes sobre estas substâncias. Objetivos: estudar a influência de Mag-p em agragados de SDS. Métodos: o efeito da diluição 12c de Mag-p sobre a estrutura de agregados de SDS foi estudada através de ressonância magnética nuclear de 13C. Resultados: O espectro de SDS e Mag-p 12c em D2O apresentou um sinal extra em 221.41 ppm, quando comparado com o espectro de SDS / D2O. O grupamento C=O group das cetonas e aldeídos absorvem por volta de 200 ppm. O Carbono da carbonila mostrou um aumento no tempo de relaxação spin-rede (T1) e fraco aumento NOE (Nuclear Overhauser Effect), uma vez que este tipo de átomo geram sinais fracos em relação aos carbonos ligados a hidrogênios. O sinal presente em 221.41 ppm foi comparável em tamanho a outros sinais do espectro, sugerindo que este sinal pode não ser devido a um arfetato experimental. Os resultados obtidos sugerem que este sinal foi pode ter sido originado pela combinação de SDS com as moléculas da alta diluição.(AU)

Synthesis of new phytogrowth-inhibitory substituted aryl-p-benzoquinones.

Reaction of [(2-alkyloxy)methyl]-1,4-dimethoxybenzene 10 (alkyl=butyl, hexyl, decyl, tridecyl, tetradecyl, hexadecyl, and octadecyl) with ceric ammonium nitrate in order to produce p-benzoquinones (=cyclohexa-2,5-diene-1,4-diones) afforded 5-[(alkyloxy)methyl]-2-(4-formyl-2,5-dimethoxyphenyl)benzo-1,4-quinones 12a-12g in yields that varied from 46 to 97%, accompanied by 2-[(alkyloxy)methyl]benzo-1,4-quinones 11a-11g in only small quantities (< or =5%). These quinones resemble the natural phytotoxic compound sorgoleone, found in Sorghum bicolor. This reaction exemplifies a general procedure for the synthesis of novel aryl-substituted p-benzoquinones. The selective effects of compounds 12a-12g, at the concentration of 5.5 ppm, on the growth of Cucumis sativus, Sorghum bicolor, Euphorbia heterophylla, and Ipomoea grandifolia were evaluated. All compounds caused some inhibition upon the aerial parts and root growth of the tested plants. The most active compound, 2-(4-formyl-2,5-dimethoxyphenyl)-5-[(tridecyloxy)methyl]-benzo-1,4-quinone (12d), caused between 3 and 18%, and 12 and 29% inhibition on the roots and aerial parts development of Cucumis sativus and Sorghum bicolor, respectively, and between 77 and 85%, and 34 and 52% inhibition on the roots and aerial parts growth of Euphorbia heterophylla and Ipomoea grandifolia, respectively.