Sousa Francielle T G, Nunes Cristina, Romano Camila Malta, Sabino Ester Cerdeira, González-Cardenete Miguel Angel
University of California-Berkeley, School of Public Health, Division of Infectious Diseases and Immunity, Berkeley, California, USA.
Universidade de São Paulo, Faculdade de Medicina, Departamento de Doenças Infecciosas e Parasitárias, São Paulo, São Paulo, Brazil.
Rev Inst Med Trop Sao Paulo. 2020 Dec 7;62:e97. doi: 10.1590/S1678-9946202062097. eCollection 2020.
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.
枞烷二萜类化合物是天然存在的植物代谢产物，具有广泛的生物学效应，包括抗菌、抗利什曼原虫、抗肿瘤、抗氧化以及抗炎活性。最近，我们发现天然铁杉醇（2）的一些类似物能有效抑制登革病毒2型（DENV-2）的复制。鉴于与登革病毒的相似性，我们设想枞烷二萜类化合物对寨卡病毒（ZIKV）也具有活性。对六种选定的（+）-脱氢枞胺（3）的半合成枞烷衍生物进行了测试。通过MTT法在Vero细胞中测定细胞毒性。通过蚀斑试验评估体外抗寨卡病毒（临床分离株，IMT17）活性。有趣的是，这些分子显示出作为抗寨卡病毒药物的潜力，EC50值范围为0.67至18.57μM，细胞毒性（CC50值）为2.56至35.09μM。18-氧代铁杉醇（8）（EC50 = 2.60μM，SI = 13.51）和12-硝基-N-苯甲酰基脱氢枞胺（9）（EC50 = 0.67μM，SI = 3.82）是活性最强的化合物，其次是12-羟基-N-对甲苯磺酰基脱氢枞胺（7）（EC50 = 3.58μM，SI = 3.20）和12-羟基-N，N-邻苯二甲酰基脱氢枞胺（5）（EC50 = 7.76μM，SI = 1.23）。据我们所知，这是关于枞烷类化合物抗寨卡病毒特性的首次报道。
