Department of Biochemistry and Microbiology, Rhodes University, PO Box 94, Grahamstown 6140, South Africa.
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Mar Drugs. 2019 Jan 16;17(1):60. doi: 10.3390/md17010060.
The temperate marine sponge, , produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo--quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a sponge species, and the first description of distinct chemotypes within a species of the family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.
温和海洋海绵 产生具有抗癌药物先导潜力的吡咯并 iminoquinone 生物碱。我们使用基于 HR-ESI-LC-MS/MS 的分子网络分析对 海绵的次生代谢产物库进行了剖析，然后进行了制备性纯化工作，以绘制七种标本提取物中新型和已知吡咯并 iminoquinone 和相关化合物的多样性。分子分类鉴定证实所有海绵均为 ，其中五个标本（化学型 I）主要产生 discorhabdins 和 tsitsikammamines。然而，令人惊讶的是，两个标本（化学型 II）表现出明显的形态和化学特征：缺乏 discorhabdins，tsitsikammamines 仅微量存在，而大量存在无支链和卤代 makaluvamines。靶向色谱分离提供了新的 makaluvamine Q、已知的 makaluvamines A 和 I、tsitsikammamine B、14-溴-7,8-去氢-3-二氢-discorhabdin C 以及相关的吡咯并 --quinones makaluvamine O 和 makaluvone。纯化的化合物在拓扑异构酶 I 抑制、DNA 嵌入和抗代谢活性测定中对人细胞系的不同活性谱。这是首次从 海绵种中分离出 makaluvamines 的报道，也是首次在 科的一个种中描述了不同的化学型。本研究为 latrunculid 海绵的假定吡咯并 iminoquinone 生物合成途径提供了新的认识。
