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.
|Original language||English (US)|
|State||Published - Oct 19 2022|
Bibliographical noteKAUST Repository Item: Exported on 2022-10-21
Acknowledgements: This research was funded by the King Abdullah University of Science and Technology, Thuwal, Jeddah, Saudi Arabia and United States International University, Nairobi, Kenya. EMT acknowledges United States International University-Africa Internal Grant No. 10-2854, and University of Nairobi, Kenya Medical Research institute, the Institute of Primate Research and King Abdullah University of Science and Technology for their support toward the successful completion of the research work.
ASJC Scopus subject areas
- Organic Chemistry