A novel method has been developed for the desymmetrization of aromatic dicarboxylic acids by employing an esterification reaction/conjugate addition of a carboxyl group to ynoates, which can trigger a coupling reaction.

We have developed a strategy to analyze the components absorbed in the plasma and brain tissue of rats after intragastric administration of Terminalia chebula Retz extracts by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–QTOF-MS). Nine components (gallic acid, methyl gallate, ferulic acid, ethyl gallate, brevifolin carboxylic acid, ellagic acid, galloflavin, arjugenin, and arjunic acid) and four metabolites were identified in plasma, and five components (ethyl gallate, brevifolin carboxylic acid, ellagic acid, arjugenin, and arjunic acid) were identified in the rat brain based on their fragmentation behaviors. The components present in the plasma were associated with the antioxidant activity of T. chebula Retz, and the components absorbed in the brain were associated with its neuro-protective effects. This approach allowed us to rapidly determine the active components of T. chebula Retz and develop a method for its quality control. This analysis method showed good resolution and high sensitivity, and is a potentially powerful tool for the determination of effective components of natural products.

Cytisine N-methylene-(5,7-dihydroxy-4'-methoxy)-isoflavone (CNF2) is a new compound isolated from the Chinese herbal medicine Sophora alopecuroides. Preliminary pharmacodynamic studies demonstrated its activity in inhibiting breast cancer cell metastasis. This study examined the pharmacokinetics, absolute bioavailability, and tissue distribution of CNF2 in rats, and combined computer-aided technology to predict the druggability of CNF2. The binding site of CNF2 and the breast cancer target HER2 were examined with molecular docking technology. Next, ACD/Percepta software was used to predict the druggability of CNF2 based on the quantitative structure-activity relationship (QSAR). Finally, a simple and effective high-performance liquid chromatography (HPLC) method was used to determine plasma pharmacokinetics and tissue distribution of CNF2 in rats. Prediction and experimental results show that compared with the positive control HER2 inhibitor SYR127063, CNF2 has a stronger binding affinity with HER2, suggesting that its efficacy is stronger; and the structure of CNF2 complies with the Lipinski's Rule of Five and has good drug-likeness. The residence time of CNF2 in rats is less than 4 hours, and the metabolic rate is relatively fast; But the absolute bioavailability of CNF2 in rats was 6.6%, mainly distributed in the stomach, intestine, and lung tissues, where the CNF2 contents were 401.20 μg/g, 144.01 μg/g, and 245.82 μg/g, respectively. This study constructed rapid screening and preliminary evaluation of active compounds, which provided important references for the development and further research of such compounds.