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].

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.

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.