Two new pregnane-type steroids from Astragalus variabilis: COX-2 inhibitory potential and structural characterization

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Astragalus variabilis is a plant source of bioactive compounds.
• Steroidal compounds are known for their diverse pharmacological activities.
• Cyclooxygenase-2 (COX-2) is a key target for anti-inflammatory drug development.

Purpose of the Study:

• To isolate and characterize novel steroidal compounds from Astragalus variabilis.
• To evaluate the COX-2 inhibitory activity of the isolated compounds.
• To investigate the binding mechanism of the new steroids with COX-2 using computational methods.

Main Methods:

• Phytochemical investigation and spectroscopic analyses (NMR, MS) for compound identification.
• In vitro cyclooxygenase (COX) inhibition assays.
• Molecular docking, molecular dynamics simulations, and MM/GBSA calculations.
• ADMET prediction for pharmacokinetic properties.

Main Results:

• Three steroidal compounds were isolated: two new pregnane-type steroids (variabilisterones A and B) and one known steroid.
• Compounds 1-3 demonstrated moderate and selective COX-2 inhibitory activity (IC50 values ~15-17 μM).
• Computational studies revealed stable binding of variabilisterones A and B within the COX-2 active site, driven by hydrophobic interactions and hydrogen bonding.

Conclusions:

• Astragalus variabilis yields novel pregnane-type steroids with selective COX-2 inhibitory potential.
• The isolated compounds exhibit anti-inflammatory properties.
• These findings support further research into A. variabilis-derived steroids as potential COX-2 inhibitors for therapeutic applications.