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

Abietane diterpenoids are naturally occurring plant metabolites with a broad spectrum of biological effects including antibacterial. antileishmanial, antitumor, antioxidant, as well as antiinfiammatory activities. Recently, we found that some analogues of natural ferruginol (2) actively inhibited dengue virus 2 (DENV-2) replication. Due to the similarity with DENY, we envisaged that abietane diteipenoids would also be active against Zika virus (ZIKV). Six selected semi-synthetic abietane derivatives of (+)-dehydroabietylatnine (3) were tested. Cytotoxicity was determined by Mn' 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 mu M. and cytotoxicity (CC50 values) from 256 to 35.09 mu M. The 18-Oxoferruginol (8) (EC50 = 2.60 mu M, SI = 13.51) and 12-nitro-N-benzoyldehydroabietylamine (9) (ECG 0.67 mu M, SI = 3.82) were the most active compounds, followed by 12-hydroxy-N-tosyldehydroabietylamine (7) (EC50 = 3.58 mu M, SI = 3.20) and 12-hydroxy-N,N-phthaloyldehydroabietylamine (5) (EC50 = 7.76 mu M, SI = 1.23). To the best of our knowledge, this is the first report on anti-Zika virus properties of abietanes.