Anti-Zika virus activity of several abietane-type ferruginol analogues

• Published in: Revista do Instituto de Medicina Tropical de São Paulo
• Main Authors: Francielle T. G. Sousa, Cristina Nunes, Camila Malta Romano, Ester Cerdeira Sabino, Miguel Angel González-Cardenete
• Format: Article in Journal/Newspaper
• Language: English
• Published: Universidade de São Paulo (USP) 2020
• Subjects: Zika; Abietane; Diterpenoid; Semi-synthesis; Anti-ZIKV activity; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1590/s1678-9946202062097; https://doaj.org/article/b1f1e5341a1344a5a0c95cdc3c07fdcd

ABSTRACT Abietane diterpenoids are naturally occurring plant metabolites with a broad spectrum of biological effects including antibacterial, antileishmanial, antitumor, antioxidant, as well as antiinflammatory activities. Recently, we found that some analogues of natural ferruginol ( 2 ) actively inhibited dengue virus 2 (DENV-2) replication. Due to the similarity with DENV, we envisaged that abietane diterpenoids would also be active against Zika virus (ZIKV). Six selected semi-synthetic abietane derivatives of (+)-dehydroabietylamine ( 3 ) were tested. Cytotoxicity was determined by MTT assay in Vero cells. In vitro anti-ZIKV (clinical isolate, IMT17) activity was evaluated by plaque assay. Interestingly, these molecules showed potential as anti-ZIKV agents, with EC50 values ranging from 0.67 to 18.57 µM, and cytotoxicity (CC50 values) from 2.56 to 35.09 µM. The 18-Oxoferruginol (8) (EC50 = 2.60 µM, SI = 13.51) and 12-nitro-N-benzoyldehydroabietylamine (9) (EC50= 0.67 µM, SI = 3.82) were the most active compounds, followed by 12-hydroxy-N-tosyldehydroabietylamine ( 7 ) (EC50 = 3.58 µM, SI = 3.20) and 12-hydroxy-N,N-phthaloyldehydroabietylamine ( 5 ) (EC50 = 7.76 µM, SI = 1.23). To the best of our knowledge, this is the first report on anti-Zika virus properties of abietanes.