Cytotoxic steroids of Gelsemium sempervirens

Area of Science:

• Natural Product Chemistry
• Organic Chemistry
• Pharmacognosy

Background:

• Gelsemium sempervirens is a plant source of bioactive compounds.
• Pregnane derivatives are a class of steroids with diverse biological activities.
• Cytotoxicity of plant-derived compounds is of interest for drug discovery.

Purpose of the Study:

• To isolate and characterize cytotoxic compounds from Gelsemium sempervirens.
• To elucidate the structures of isolated pregnane derivatives using spectroscopic methods.
• To evaluate the cytotoxic potential of isolated compounds and known indole alkaloids.

Main Methods:

• Methanol extraction of Gelsemium sempervirens stem.
• Isolation and purification of chemical constituents.
• 13C NMR, Heteronuclear 2D correlation, and selective INEPT experiments for structural elucidation.
• Cytotoxicity testing against KB and P-388 cell lines.

Main Results:

• Isolation of a new pregnane derivative, 12 beta-hydroxy-5 alpha-pregn-16-ene-3,20-dione, and a known derivative, 12 beta-hydroxy-pregna-4,16-diene-3,20-dione.
• These pregnane derivatives were identified as the principal cytotoxic entities.
• Structural assignments were confirmed and revised using advanced NMR techniques.
• Nine indole alkaloids from the same plant extract showed no significant cytotoxicity.

Conclusions:

• 12 beta-hydroxy-5 alpha-pregn-16-ene-3,20-dione and 12 beta-hydroxy-pregna-4,16-diene-3,20-dione are potent cytotoxic agents from Gelsemium sempervirens.
• Advanced NMR methods were crucial for accurate structural determination and revision of assignments.
• The cytotoxic activity is primarily associated with the isolated pregnane derivatives, not the tested indole alkaloids.