Fractionation Coupled to Molecular Networking: Towards Identification of Anthelmintic Molecules in Terminalia leiocarpa (DC.) Baill

Terminalia leiocarpa is a medicinal plant widely used in ethnoveterinary medicine to treat digestive parasitosis whose extracts were shown to be active against gastrointestinal nematodes of domestic ruminants. The objective of our study was to identify compounds responsible for this activity. Column fractionation was performed, and the activity of the fractions was assessed in vitro on Haemonchus contortus and Caenorhabditis elegans as well as their cytotoxicity on WI38 fibroblasts. Two fractions were the most active on both nematode models and less cytotoxic. LC-MS/MS analysis and manual dereplication coupled to molecular networking allowed identification of the main compounds: ellagic acid and derivatives, gallic acid, astragalin, rutin, quinic acid, and fructose. Other potentially identified compounds such as shikimic acid, 2,3-(S)-hexahydroxydiphenoyl-D-glucose or an isomer, quercetin-3-O-(6-O-galloyl)-β-D-galactopyranoside or an isomer, and a trihydroxylated triterpenoid bearing a sugar as rosamultin are reported in this plant for the first time. Evaluation of the anthelmintic activity of the available major compounds showed that ellagic and gallic acids were the most effective in inhibiting the viability of C. elegans. Their quantification in fractions 8 and 9 indicated the presence of about 8.6 and 7.1 µg/mg ellagic acid and about 9.6 and 2.0 µg/mg gallic acid respectively. These concentrations are not sufficient to justify the activity observed. Ellagic acid derivatives and other compounds that were found to be positively correlated with the anthelmintic activity of the fractions may have additive or synergistic effects when combined, but other unidentified compounds could also be implicated in the observed activity.     

Futtermittel

Ohne Zusammenfassung     

Untersuchung von Obst und Obstkonserven

Ohne Zusammenfassung     

Evgeniĭ Invievich Givargizov (On the occasion of his 75th Birthday)

Crystallography Reports -     

Supermembranes

An example is given of the spontaneous breaking of D = 4, N = 2 global supersymmetry down to N = 1. The example is a four-dimensional membrane in a six-dimensional supersymmetric gauge theory. The effective low-energy action for the membrane is a generalization of the Green—Schwarz covariant action.     

Exploring the Potential of Multinuclear Solid-State 1H, 13C,and 35Cl Magnetic Resonance To Characterize Static and Dynamic Disorder in Pharmaceutical Hydrochlorides

Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field ³⁵Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride ( 1 ), static disorder in promethazine hydrochloride ( 2 ), and trifluoperazine dihydrochloride ( 3 ). In all structures, the presence of crystallographic disorder was confirmed by ¹³C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3 , ¹H solid-state NMR provided additional confirmation. Applying ³⁵Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3 , while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from ¹H, ¹³C, and ³⁵Cl NMR, we show that 3 exhibits a unique case of disorder involving the ⁺N−H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.     

Fractal random walks

We consider a class of random walks (on lattices and in continuous spaces) having infinite mean-squared displacement per step. The probability distribution functions considered generate fractal self-similar trajectories. The characteristic functions (structure functions) of the walks are nonanalytic functions and satisfy scaling equations.Supported by the Commonwealth Scientific and Industrial Research Organization (Australia).Supported by the Xerox Corporation.Supported in part by a grant from DARPA.