Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

ABSTRACT: Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against Zika virus, Dengue virus, Herpes virus simplex type 1, and Chikungunya virus are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC50 between 5.0 and 10.0 μM against Colombian Zika virus strains and EC50 = 9.8 μM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC50 = 1.4 μM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.

• Autores: González Cardenete, Miguel Ángel; Hamulić, Damir; Miquel Leal, Francisco; González Zapata, Natalia; Jiménez Jarava, Orlando José; Miranda Brand, Yaneth; Restrepo Mendez, Laura; Martínez Gutiérrez, Marlen; Betancur Galvis, Liliana Amparo; Marín, María
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/43338
• Acceso en línea: https://hdl.handle.net/10495/43338
• Palabra clave: Abietanos; Abietanes; Antivirales; Antiviral Agents; Virus Chikungunya; Chikungunya virus; Replicación Viral; Virus Replication; Virus; Viruses; Infección por el Virus Zika; Zika Virus Infection; https://id.nlm.nih.gov/mesh/D045784; https://id.nlm.nih.gov/mesh/D000998; https://id.nlm.nih.gov/mesh/D002646; https://id.nlm.nih.gov/mesh/D014779; https://id.nlm.nih.gov/mesh/D014780; https://id.nlm.nih.gov/mesh/D000071243
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/