Dracomolphin A-E, new lignans from Dracocephalum moldavica

Area of Science:

• Phytochemistry
• Natural Products Chemistry
• Medicinal Chemistry

Background:

• Dracocephalum moldavica is a plant species known for its diverse secondary metabolites.
• Lignans are a class of phenolic compounds with a wide range of biological activities.
• Investigating the chemical constituents of medicinal plants can lead to the discovery of novel therapeutic agents.

Purpose of the Study:

• To isolate and characterize new lignan compounds from the aerial parts of Dracocephalum moldavica.
• To evaluate the bioactivity of the isolated compounds, focusing on Nrf2 transcriptional activation and anti-cancer properties.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation of new lignans using Nuclear Magnetic Resonance (NMR) and High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS).
• Separation and stereochemical determination of dracomolphin A isomers using chiral High-Performance Liquid Chromatography (HPLC) and Circular Dichroism (CD) spectroscopy.
• Bioactivity screening, including Nrf2 transcriptional activation assays and cell viability assays on lung cancer cell lines.

Main Results:

• Eight new lignans, designated dracomolphin A-E (1-8), along with eight known lignans (9-16), were isolated.
• The structures of the new lignans were determined, with dracomolphin A (1-4) characterized by a unique 5-membered ketal ring.
• Chiral HPLC successfully separated the four stereoisomers of dracomolphin A, and their configurations were confirmed by CD spectra.
• Compounds 1-4, 6, 7, 12, 15, and 16 demonstrated potential as Nrf2 transcriptional activators.
• Dracomolphin E (8) exhibited cytotoxic effects on NCI-H292 lung cancer cells, inducing apoptosis.

Conclusions:

• The study successfully identified novel lignan structures from Dracocephalum moldavica.
• Several isolated lignans, particularly dracomolphins A-D, show promise as Nrf2 transcriptional activators, suggesting potential therapeutic applications in diseases involving oxidative stress.
• Dracomolphin E displays significant anti-cancer activity against lung cancer cells, warranting further investigation for its development as an anti-cancer agent.