Cage-like monoterpenoid indole alkaloids with antimicrobial activity from Alstonia scholaris

Three new cage-like monoterpenoid indole alkaloids, scholarisines T–V (1–3), together with three known analogues 4–6 were isolated from the leaves of Alstonia scholaris. Among them, 2 represents a unique degraded derivative, whereas 3 shares a rare 5,16-seco lactone scaffold. The structures were mainly established by extensive spectroscopic data analyses, and their plausible biosynthesis pathway from picrinine were proposed. Compared with positive control cefotaxime, alkaloid 2 showed remarkable antibacterial activity against Bacillus subtilis with an MIC value of 3.12?μg/mL, whereas 1–3 exhibited significant antibacterial effects on Escherichia coli with an MIC value of 0.78?μg/mL.     

Simultaneous quantitation of the diastereoisomers of scholarisine and 19‐epischolarisine,vallesamine, and picrinine in rat plasma by supercritical fluid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

Dengtaiye tablet has been used to treat chronic bronchitis cough. Scholarisine, 19‐epischolarisine, vallesamine, and picrinine are the representative constituents of Dengtaiye. A rapid and sensitive assay based on supercritical fluid chromatography with tandem mass spectrometry has been developed and validated for the determination of the diastereoisomers of scholarisine and 19‐epischolarisine, vallesamine, and picrinine in rat plasma using lamotrigine as internal standard. The analysis in a run time of only 6 min was performed on an ACQUITY UPC² Trefoil^TM BEH 2‐EP column (3.0 × 150 mm, 2.5 μm) at 50ºC. The mobile phase consisting of carbon dioxide and methanol (2 mM ammonium formate) was performed as follows: 15% methanol (2 mM ammonium formate) maintained at 0–2 min, 15–19% methanol (2 mM ammonium formate) at 2–4 min, 19–15% methanol (2 mM ammonium formate) at 4–6 min. The flow rate was 1.50 mL/min. The assay was linear over the concentration ranges 50–10000 pg/mL for scholarisine, 19‐epischolarisine, vallesamine, and picrinine with corresponding lower limits of quantitation of 50 pg/mL. Intra‐ and interday precisions were in the range 1.42–12.85% with accuracies in the range –11.71–2.48%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 108 mg/kg Dengtaiye tablet to rats.