Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Buxus sempervirens (boxwood) is a source of structurally diverse alkaloids with potential medicinal properties.
• Previous research has identified various Buxus alkaloids, but novel structures and bioactivities continue to be discovered.

Purpose of the Study:

• To conduct an extensive phytochemical investigation of the methanol extract of Buxus sempervirens twigs and leaves.
• To isolate, identify, and characterize new Buxus alkaloids.
• To evaluate the bioactivity of the isolated compounds, particularly their protective effects in a doxorubicin-induced cardiac injury model.

Main Methods:

• Phytochemical analysis of the methanol extract using High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS) and Nuclear Magnetic Resonance (NMR) spectroscopy.
• Structure elucidation aided by detailed spectroscopic data analysis and quantum chemical NMR calculations.
• In vitro bioactivity assessment using a doxorubicin-induced cardiac injury model.

Main Results:

• Isolation and identification of 17 Buxus alkaloids, with 12 novel compounds designated as buxusemines A-L (1-12).
• Characterization of unique structural motifs in new alkaloids, including a spiro[4.6]undecatriene moiety (buxusemine A), an additional five-membered ring (buxusemines B-C), and an epoxy motif (buxusemines D-F).
• Buxusemine F (6) and buxanoldine (17) demonstrated superior protective effects against doxorubicin-induced cardiotoxicity compared to the positive control, cyclovirobuxinum D.

Conclusions:

• The study successfully identified a significant number of new Buxus alkaloids from Buxus sempervirens, expanding the known chemical diversity of this genus.
• Buxusemine F and buxanoldine show promising cardioprotective potential, warranting further investigation for therapeutic applications in managing drug-induced cardiac injury.