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

  • J Nat Prod. 2022 Aug 26;85(8):2044-2051. doi: 10.1021/acs.jnatprod.2c00464.
Miguel A González-Cardenete  1 ,  Damir Hamulić  1 ,  Francisco J Miquel-Leal  1 ,  Natalia González-Zapata  1 ,  Orlando J Jimenez-Jarava  2 ,  Yaneth M Brand  2 ,  Laura C Restrepo-Mendez  3 ,  Marlen Martinez-Gutierrez  3  4 ,  Liliana A Betancur-Galvis  2 ,  Maria L Marín  1
Affiliations
  • 1. Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Científicas, Avda de los Naranjos s/n, 46022 Valencia, Spain.
  • 2. Grupo de Investigaciones Dermatológicas, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia.
  • 3. Grupo de Investigación en Ciencias Animales-GRICA, Universidad Cooperativa de Colombia, 680001 Bucaramanga, Colombia.
  • 4. Línea de Descubrimiento y Evaluación de Compuestos Antivirales, Grupo de Investigación en Microbiología Básica y Aplicada (MICROBA), Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia.
PMID: 35969814 DOI: 10.1021/acs.jnatprod.2c00464
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.