Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran 1983969411, Iran.
GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany.
Mar Drugs. 2020 Jul 16;18(7):366. doi: 10.3390/md18070366.
The geographic position, highly fluctuating sea temperatures and hypersalinity make Persian Gulf an extreme environment. Although this unique environment has high biodiversity dominated by invertebrates, its potential in marine biodiscovery has largely remained untapped. Herein, we aimed at a detailed analysis of the metabolome and bioactivity profiles of the marine sponge collected from the northeast coast of the Persian Gulf in Iran. The crude extract and its Kupchan subextracts were tested in multiple in-house bioassays, and the crude extract and its CHCl-soluble portion showed in vitro antibacterial activity against Methicillin-resistant (MRSA) and (Efm). A molecular networking (MN)-based dereplication strategy by UPLC-MS/MS revealed the presence of phospholipids and steroids, while H NMR spectroscopy indicated the presence of additional metabolites, such as diketopiperazines (DKPs). Integrated MN and H NMR analyses on both the crude and CHCl extracts combined with an antibacterial activity-guided isolation approach afforded eight metabolites: a new diketopiperazine, (-)-cyclo(--Hyp--Ile) (); a known diketopiperazine, cyclo(--Hyp--Phe) (); two known phospholipids, 1--hexadecyl--glycero-3-phosphocholine () and 1--octadecanoyl--glycero-3-phosphocholine (); two known steroids, 3β-hydroxycholest-5-ene-7,24-dione () and (22)-3β-hydroxycholesta-5,22-diene-7,24-dione (); two known monoterpenes, loliolide () and 5--loliolide (). The chemical structures of the isolates were elucidated by a combination of NMR spectroscopy, HRMS and [α] analyses. All compounds were tested against MRSA and Efm, and compound showed moderate antibacterial activity against MRSA (IC value 70 μg/mL). This is the first study that has dealt with chemical and bioactivity profiling of leading to isolation and characterization of pure sponge metabolites.
波斯湾的地理位置、波动剧烈的海水温度和高盐度使其成为一个极端环境。尽管这种独特的环境拥有以无脊椎动物为主的高生物多样性，但它在海洋生物发现方面的潜力在很大程度上尚未被开发。在此，我们旨在对从伊朗波斯湾东北海岸采集的海洋海绵进行详细的代谢组学和生物活性分析。粗提取物及其 Kupchan 亚提取物在多个内部生物测定中进行了测试，粗提取物及其 CHCl 可溶部分显示出对耐甲氧西林金黄色葡萄球菌 (MRSA)和 (Efm)的体外抗菌活性。基于 UPLC-MS/MS 的分子网络 (MN) 去重策略揭示了磷脂和类固醇的存在，而 1 H NMR 光谱表明存在其他代谢物，如二酮哌嗪 (DKP)。对粗提取物和 CHCl 提取物进行的综合 MN 和 1 H NMR 分析，以及基于抗菌活性的分离方法，得到了 8 种代谢物：一种新的二酮哌嗪，(-)-环(-Hyp--Ile) (); 一种已知的二酮哌嗪，环(-Hyp--Phe) (); 两种已知的磷脂，1--十六烷基--甘油-3-磷酸胆碱 () 和 1--十八烷酰基--甘油-3-磷酸胆碱 (); 两种已知的类固醇，3β-羟基胆甾-5-烯-7,24-二酮 () 和 (22)-3β-羟基胆甾-5,22-二烯-7,24-二酮 (); 两种已知的单萜，loliolide () 和 5--loliolide (). 利用 NMR 光谱、高分辨质谱和 [α] 分析相结合的方法，阐明了分离物的化学结构。所有化合物均针对 MRSA 和 Efm 进行了测试，化合物 对 MRSA 表现出中等抗菌活性（IC 值为 70 μg/mL）。这是首次对 进行化学和生物活性分析，导致了海绵代谢物的分离和鉴定。
