Laboratório de Produtos Naturais, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Laboratório de Farmacognosia, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Mar Drugs. 2019 Jan 16;17(1):57. doi: 10.3390/md17010057.
The marine sponge , collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge's hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene () with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (), kerlinic acid methyl ester (), annonene (), and 6-hydroxyannonene (). They differ in their stereochemistry, since these diterpenes are characterized by a ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a relationship (type ). The diterpenes have a ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a relationship (type /). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC) values lower than 25 μM. The evaluation of the potential anti-herpes activity against type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound , since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.
从巴西南部采集的海洋海绵因体外抗人非小细胞肺癌（A549）增殖作用筛选结果而被选中进行详细研究，并具有抗疱疹活性 1 型（KOS 和 29R 株）的乙醇提取物。海绵正己烷部分的分离和化学研究导致了六种 clerodane 二萜的分离和结构阐明。主要成分被鉴定为已经报道的 raspailol ()，从同一属的海绵中分离出来，从新西兰采集。通过高分辨率质谱 (HRMS) 和 1D 和 2D 核磁共振波谱 (NMR) 实验建立了具有重排骨架的新二萜 ()的结构，并在这里命名为 raspadiene。此外，从植物中分离出的 clerodane 二萜的四个异构体也被阐明，即 kerlinic 酸 ()、kerlinic 酸甲酯 ()、annonene ()和 6-羟基annonene ()。它们在立体化学上有所不同，因为这些二萜的特征在于 decalin 部分的环融合以及 C-8 和 C-9 处两个甲基基团的相对构型为 关系（type ）。 二萜的 decalin 部分有一个环融合，C-8 和 C-9 处的两个甲基基团呈 关系（type /）。评估了分离得到的化合物对人肺癌细胞系 A549 的潜在增殖抑制作用，发现具有 C-6 位羟基的二萜表现出中等细胞毒性活性，50%抑制浓度 (IC) 值低于 25 μM。对 1 型（HSV-1、KOS 和 29R 株）的潜在抗疱疹活性的评价表明，新化合物 显示出更有希望的结果，因为它分别抑制 HSV-1（KOS 和 29R 株）的复制率为 83%和 74%。
