[Two novel cephalotaxine-type alkaloids from Cephalotaxus sinensis]

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Cephalotaxus sinensis is a plant source of bioactive alkaloids.
• Cephalotaxine-type alkaloids have shown diverse biological activities.
• Understanding the chemical constituents and bioactivity of C. sinensis is important for drug discovery.

Purpose of the Study:

• To isolate and identify cephalotaxine-type alkaloids from Cephalotaxus sinensis.
• To characterize novel compounds using advanced spectroscopic techniques.
• To evaluate the inhibitory effects of isolated alkaloids on nuclear factor kappa B (NF-κB) transcription.

Main Methods:

• Isolation of alkaloids using silica gel, octadecyl-silica (ODS), Sephadex LH-20, and semi-preparative high-performance liquid chromatography (HPLC).
• Structure elucidation of new compounds employing high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD).
• Assessment of NF-κB transcription inhibition using half-maximal inhibitory concentration (IC50) assays.

Main Results:

• Nine cephalotaxine-type alkaloids were isolated: 8-oxodeoxyharringtonine (1), 8-oxonordeoxyharringtonine (2), cephafortunine A (3), 8-oxocephalotaxine (4), deoxyharringtonine (5), acetylcephalotaxine (6), cephalotaxine (7), epicephalotaxine (8), and cephalotaxinone (9).
• Compounds 1 and 2 were identified as novel, with their structures confirmed by HR-ESI-MS, NMR, and ECD.
• Compounds 1, 2, 3, and 5 exhibited significant inhibition of NF-κB transcription, with IC50 values ranging from 1.46 ± 0.17 to 7.84 ± 0.51 μmol·L−1.

Conclusions:

• The study successfully isolated and characterized nine cephalotaxine alkaloids from C. sinensis, including two new compounds.
• The identified alkaloids, particularly compounds 1, 2, 3, and 5, possess potent NF-κB inhibitory activity.
• These findings suggest that C. sinensis alkaloids are promising candidates for developing anti-inflammatory or anticancer agents targeting the NF-κB pathway.