Amaya García Fabián, Cirne-Santos Claudio, de Souza Barros Caroline, Pinto Ana Maria, Sanchez Nunez Maria Leonisa, Laneuville Teixeira Valeria, Resende Jackson A L C, Ramos Freddy A, Paixão Izabel C N P, Castellanos Leonardo
Universidad Nacional de Colombia-Sede Bogotá, Facultad de Ciencias, Departamento de Química, Bogotá D.C. 111321, Colombia.
Instituto de Biologia, Universidade Federal Flumimense, Niterói 24020-141, RJ, Brazil.
J Nat Prod. 2021 Apr 23;84(4):1373-1384. doi: 10.1021/acs.jnatprod.1c00199. Epub 2021 Apr 6.
Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone () and (1,7,8,11)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (), isolated from genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound showed an EC = 0.92 ± 0.08 μM and SI = 820 against ZIKV.
褐藻和软珊瑚是多拉贝拉烷二萜的主要海洋来源。人们已对从藻类中分离出的多拉贝拉烷的抗病毒活性进行了研究，而从软珊瑚中分离出的多拉贝拉烷则几乎未被研究。在这项工作中，构建了一个由5种天然衍生物和21种半合成衍生物组成的多拉贝拉烷二萜集合，并测试了它们对寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV）的抗病毒活性。从软珊瑚属中分离出的多拉贝拉三烯酮（）和（1,7,8,11）-7,8-环氧-13-酮-多拉贝拉-3,12（18）-二烯（），通过烯丙基氧化、还原、酸催化环氧开环和乙酰化等反应，用于获得21种多拉贝拉烷和多拉司坦二萜。所有化合物均通过一维和二维核磁共振、质谱和X射线衍射实验相结合的方法进行鉴定。测试了对Vero细胞的细胞毒性以及对ZIKV和CHIKV的抗病毒活性，以计算半数最大有效浓度（EC）和选择性指数（SIs）。一般来说，含氧官能团的添加提高了多拉贝拉烷和多拉司坦二萜对ZIKV和CHIKV复制的生物活性。化合物对ZIKV的EC = 0.92±0.08μM，SI = 820。
