Anti-HIV Ermiasolides from Croton megalocarpus

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5β-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5β,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5β-Hydroxy-8H-β-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5β-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC₅₀ = 0.002 µg/mL. On the other hand, 5β-Hydroxy-8H-β-eudesm-7(11)-en-12,8-olide (3) and 5β,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC₅₀ = 0.04 µg/mL and 69.5% at IC₅₀ = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease.