Olean-18-ene triterpenoids from Celastraceae species inhibit HIV replication targeting NF-kB and Sp1 dependent transcription

• Published in: European journal of medicinal chemistry 2012-06, Vol.52, p.295-303
• Main Authors: Osorio, Alex A., Muñóz, Alejandro, Torres-Romero, David, Bedoya, Luis M., Perestelo, Nayra R., Jiménez, Ignacio A., Alcamí, José, Bazzocchi, Isabel L.
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Anti-HIV Agents - toxicity; Biological and medical sciences; Biological Products - pharmacology; Biological Products - toxicity; Cassine xylocarpa; Celastraceae - chemistry; Celastraceae species; Cell Line; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus; Lymphocytes - drug effects; Lymphocytes - virology; Maytenus jelskii; Medical sciences; Miscellaneous; Models, Molecular; Molecular Conformation; NF-kappa B - metabolism; Olean-18-ene triterpenes; Pharmacology. Drug treatments; Sp1 Transcription Factor - metabolism; Structure-Activity Relationship; Terpenes - chemical synthesis; Terpenes - chemistry; Terpenes - pharmacology; Terpenes - toxicity; Transcription inhibitors; Transcription, Genetic - drug effects; Virus Replication - drug effects
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.03.035

In the present study we report the isolation of nine new olean-18-ene triterpenes (1–9), along with three known ones (10–12), from Cassine xylocarpa and Maytenus jelskii. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques (COSY, ROESY, HSQC and HMBC), and spectrometric methods. The natural compounds and derivatives 13–15 have been tested for their potential as inhibitors of human immunodeficiency virus type 1 replication. Five compounds from this series displayed potent antiviral activity with IC50s in the micromolar range (1, 3, 4, 7 and 8) being 1 and 8 the most active compounds. The target of these compounds was different from antiretroviral drugs currently licensed as they act as inhibitors of enhancer-dependent transcription. The structure–activity relationships were established based on the regiosubstitution and oxidation degree of the triterpene scaffold, revealing that these aspects were able to modulate the selectivity and intensity of HIV inhibition. A new series of olean18-ene triterpenoids isolated from Celastraceae species, were able to successfully inhibit HIV transcription. [Display omitted] ► A series of new olean-18-ene triterpenes were isolated from Celastraceae species. ► Five compounds display potent anti-HIV effect with IC50 in the μM range. ► These compounds act as inhibitors of NF-kB and Sp1 dependent HIV transcription. ► The regiosubstitution and oxidation degree of triterpene modulate the activity.