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

Author(s)

Francielle T. G. Sousa ; Cristina Nunes ^[2] ; Camila Malta Romano ; Ester Cerdeira Sabino ; Miguel Angel González-Cardenete ^[5]

• Document type: Journal article
• Source: Revista do Instituto de Medicina Tropical de São Paulo; v. 62, 2020-12-07.

Abstract

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. (AU)

• FAPESP's process: 13/01690-0 - Establishment of an in vitro model of vascular permeability evaluation to study the hemorrhagic dengue fever pathogenesis and screening of compounds with therapeutic potential
• Grantee: Ester Cerdeira Sabino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/03859-9 - Clinical, serological and virological characteristics of Dengue virus serotype 2 (DENV-2) infection in a cohort previously exposed to serotype 1
• Grantee: Camila Malta Romano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/01702-9 - Evaluation of endothelial permeability to study dengue pathogenesis and screen compounds with therapeutic potential
• Grantee: Francielle Tramontini Gomes de Sousa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral