Characterization of anti-Coxsackie virus B3 constituents of Radix Astragali by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

To profile the anti-Coxsackie virus B3 constituents of Radix Astragali, an HPLC-DAD-MS(n) analytical method, combined with an in vivo test, has been developed to identify the constituents of the active part, which has been demonstrated to have potency to inhibit the proliferation of virus in cardiac muscle, alleviate infraction in heart and elevate the survival rate of the animal. By comparing their retention time and MS data with those obtained from the authentic compounds and the published data, a total of 19 compounds, including 11 isoflavonoids and eight saponins, were identified, among which one pterocarpane glucoside was reported for the first time. The present study provides an approach to rapidly screening bioactive constituents in traditional Chinese medicines.

Determination of two metabolites of calycosin-7-O-beta-D-glucopyranoside in rat urine by HPLC.

A simple and specific analytical method for the simultaneous determination of the two metabolites of calycosin-7-O-beta-D-glucopyranoside, calycosin-7-O-beta-D-glucuronic acid methyl ester (M-1) and calycosin (M-2), in rat urine was developed using high-performance liquid chromatography. Quercetin was employed as an internal standard. The correlation coefficients of the calibration curves were higher than 0.999; both intra- and inter-day precisions of two metabolites were determined and their RSD did not exceed 10%. The accuracy and linear range were investigated in detail. The cumulative urinary excretions of two metabolites were measured.

Complete NMR spectral assignments of two new iridoid diastereoisomers from the flowers of Plumeria rubra L. cv. acutifolia.

Two new iridoid diastereoisomers (1, 2), together with five known compounds, were isolated from the flowers of Plumerian rubra L. cv. acutifolia. Their structures were elucidated by the means of in-depth spectroscopic and mass-spectrometric analyses, particularly 1D and 2D NMR spectroscopy.

[Spectroscopic studies of aripiprazole].

The ultraviolet spectrum (UV), infrared spectrum (IR), nuclear magnetic resonance (NMR) and mass spectrum (MS) of aripiprazole, a new antipsychotic drug, were reported and interpreted. The structure of aripiprazole in solution was studied according to the UV spectra detected in solution with different pH values. The vibrations of functional groups of this compound in IR and the isotopic ion peaks in MS were discussed. Moreover, the 2D-NMR techniques, including 1H-1H correlation spectroscopy (1H-1H cosy), heteronuclear single-quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC), were used to deduce the structure of this compound. All the 1H NMR and 13C NMR signals were assigned. Especially, the ten different methylenes in this structure were analyzed according to the chemical shifts, coupling constants and correlations in 2D-NMR spectrum. By all these spectral techniques, the structure of aripiprazole was identified.

Identification of 3-substituted-6-(1-(1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline derivatives as highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitors via metabolite profiling-based structural optimization.

c-Met/HGF signaling pathway plays an important role in cancer progression, and it was considered to be related to poor prognosis and drug resistance. Based on metabolite profiling of (S)-7-fluoro-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)ethyl)quinoline (1), a series of 2-substituted or 3-substituted-6-(1-(1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline derivatives was rationally designed and evaluated. Most of the 3-substituted derivatives not only exhibited potent activities in both enzymatic and cellular assays, but also were stable in liver microsomes among different species (human, rat and monkey). SAR investigation revealed that introducing of N-methyl-1H-pyrazol-4-yl group at the 3-position of quinoline moiety is beneficial to improve the inhibitory potency, especially in the cellular assays. The influence of fluorine atom at 7-position or 5, 7-position of quinoline moiety and substituents at the 6-position of triazolo[4,5-b]pyrazine core on overall activity is not very significant. Racemate 14, an extremely potent and exquisitely selective c-Met inhibitor, demonstrated favorable pharmacokinetic properties in rats, no significant AO metabolism, and effective tumor growth inhibition in c-Met overexpressed NSCLC (H1993 cell line) and gastric cancer (SNU-5 cell line) xenograft models. Docking analysis indicated that besides the typical interactions of most selective c-Met inhibitors, the intramolecular halogen bond and additional hydrogen bond interactions with kinase are beneficial to the binding. These results may provide deep insight into potential structural modifications for developing potent c-Met inhibitors.