Isoxazole and Pyrazole Derivatives of 28‐Oxo‐Allobetulone Target Viral Membrane Glycoprotein Hemagglutinin

A series of [2,3]-isoxazoles and pyrazole annulated with the A-ring of lupane, oleanane, and ursane type triterpenoids was synthesized and screened for antiviral activity. It was found that 28-oxo-allobetulone isoxazole 4 with IC₅₀ 7.3 μM (SI 86) and pyrazole 5 with IC₅₀ 62.1 μM (SI 10) demonstrated a high inhibitory activity against Flu A/Puerto Rico/8/34 (H1N1) strain virus. The compounds 4 and 5 appeared to be the most active at the earlier stages of the viral cycle (0-2 h post infecting). No inhibiting effect of compounds 4 and 5 on the fusogenic activity of hemagglutinin HA has been detected, but the compounds prevented the binding of virions with the cell receptor. According to the results of molecular docking, compounds 4 and 5 preferentially bound to the interface between HA1 and HA2 subunits of hemagglutinin, near the heptad repeat domain.