GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, Kiel 24106, Germany.
Senckenberg Research Institute and Natural History Museum, Senckenberganlage 25, Frankfurt D-60325, Germany.
Mar Drugs. 2020 Feb 11;18(2):107. doi: 10.3390/md18020107.
sponges represent a rich source of discorhabdin-type pyrroloiminoquinone alkaloids, a few of which comprise a dimeric structure. The anticancer-activity-guided isolation of the -hexane subextract of the Antarctic deep-sea sponge yielded the known compound (-)-(1R,2R,6R,8S,6'S)-discorhabdin B dimer () and two new derivatives, (-)-(1S,2R,6R,8S,6'S)-discorhabdin B dimer (2) and (-)-(1R,2R,6R,8S,6'S)-16',17'-dehydrodiscorhabdin B dimer (3). The chemical structures of compounds - were elucidated by means of HR-ESIMS, NMR, [], ECD spectroscopy, and a comparison with the previously reported discorhabdin analogs. Compounds and showed significant in vitro anticancer activity against the human colon cancer cell line (HCT-116), with IC values of 0.16 and 2.01 µM, respectively. Compared to monomeric discorhabdins, dimeric discorhabdins are very rare in Nature. This study adds two new discorhabdin dimers ( and ) to this small pyrroloiminoquinone subfamily. This is also the first report of compound as a natural product and the first assessment of its in vitro anticancer activity.
海绵代表了丰富的 discorhabdin 型吡咯并亚氨基喹酮生物碱来源，其中一些具有二聚体结构。基于抗癌活性导向，从南极深海海绵 中分离得到 -己烷亚提取物，得到了已知化合物 (-)-(1R,2R,6R,8S,6'S)-discorhabdin B 二聚体 () 和两个新衍生物 (-)-(1S,2R,6R,8S,6'S)-discorhabdin B 二聚体 (2) 和 (-)-(1R,2R,6R,8S,6'S)-16',17'-脱氢 discorhabdin B 二聚体 (3)。通过高分辨电喷雾质谱 (HR-ESIMS)、NMR、[]、ECD 光谱以及与先前报道的 discorhabdin 类似物的比较，确定了化合物 - 的化学结构。化合物 和 对人结肠癌细胞系 (HCT-116) 表现出显著的体外抗癌活性，IC 值分别为 0.16 和 2.01 µM。与单体 discorhabdins 相比，二聚体 discorhabdins 在自然界中非常罕见。本研究在这一小吡咯并亚氨基喹酮亚家族中增加了两个新的 discorhabdin 二聚体 ( 和 )。这也是首次报道化合物 为天然产物，并首次评估其体外抗癌活性。
