Alkaloid constituents from Viola tianschanica

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Viola tianschanica is a plant species known for its potential chemical diversity.
• Alkaloids are a significant class of natural products with diverse biological activities.
• Understanding the chemical constituents of medicinal plants is crucial for drug discovery.

Purpose of the Study:

• To isolate and characterize novel alkaloids from Viola tianschanica.
• To determine the structures and absolute configurations of the isolated compounds.
• To evaluate the inhibitory effects of these alkaloids on menin-mixed lineage leukemia 1 (MLL1) protein-protein interactions.

Main Methods:

• Isolation of alkaloids using chromatographic techniques.
• Structure elucidation using comprehensive spectroscopic analyses (1D, 2D-NMR, (+)HRESIMS).
• Determination of absolute configurations via experimental and calculated electronic circular dichroism (ECD) spectra.
• In vitro assays to measure menin-MLL1 protein-protein interaction inhibition.

Main Results:

• Eighteen previously undescribed alkaloids, designated tishaviolamines A-J (including eight pairs of enantiomers), were isolated.
• Two known benzylisoquinoline alkaloids, (-)-bicuculline and (-)-corlumine, were also identified.
• Tishaviolamines A-E exhibited novel skeletal structures previously unreported in the literature.
• The absolute configurations of the enantiomeric pairs were successfully assigned.
• Preliminary evaluation of menin-MLL1 protein-protein interaction inhibitory activity was conducted for the isolated compounds.

Conclusions:

• Viola tianschanica is a rich source of structurally diverse alkaloids, including novel chemical scaffolds.
• The established methodologies enabled the full characterization of these complex natural products.
• The isolated alkaloids, particularly tishaviolamines A-E, represent potential leads for further investigation in MLL1-targeted therapies.