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 EC 50 between 5.0 and 10.0 μM against Colombian Zika virus strains and EC 50 = 9.8 μM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC 50 = 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.

similar chemistry. The combined findings indicate that these abietane-diterpenoid natural product analogues offer a source of novel bioactive molecules with promising pharmacological and drug-likeness properties. ASSOCIATED CONTENT Supporting Information Available: Complete experimental details for the synthesis of compounds 7 and 9-16, including copies of 1 H NMR and 13 C NMR spectra, and for all the biological assays. A list with the complete results of the docking studies carried out on the analyzed targets and SMILES codes is also available in the S.I.