Institute of Pharmacology and Toxicology, Technische Universität Dresden, Dresden 01307, Germany.
Department of Pharmacy, National Pirogov Memorial Medical University, Vinnytsya 21018, Ukraine.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110566. doi: 10.1016/j.msec.2019.110566. Epub 2019 Dec 17.
Marine demosponges of the Verongiida order are considered a gold-mine for bioinspired materials science and marine pharmacology. The aim of this work was to simultaneously isolate selected bromotyrosines and unique chitinous structures from A. aerophoba and to propose these molecules and biomaterials for possible application as antibacterial and antitumor compounds and as ready-to-use scaffolds for cultivation of cardiomyocytes, respectively. Among the extracted bromotyrosines, the attention has been focused on aeroplysinin-1 that showed interesting unexpected growth inhibition properties for some Gram-negative clinical multi-resistant bacterial strains, such as A. baumannii and K. pneumoniae, and on aeroplysinin-1 and on isofistularin-3 for their anti-tumorigenic activity. For both compounds, the effects are cell line dependent, with significant growth inhibition activity on the neuroblastoma cell line SH-SY5Y by aeroplysinin-1 and on breast cancer cell line MCF-7 by isofistularin-3. In this study, we also compared the cultivation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) on the A. aerophoba chitinous scaffolds, in comparison to chitin structures that were pre-coated with Geltrex™, an extracellular matrix mimetic which is used to enhance iPSC-CM adhesion. The iPSC-CMs on uncoated and pure chitin structures started contracting 24 h after seeding, with comparable behaviour observed on Geltrex-coated cell culture plates, confirming the biocompatibility of the sponge biomaterial with this cell type. The advantage of A. aerophoba is that this source organism does not need to be collected in large quantities to supply the necessary amount for further pre-clinical studies before chemical synthesis of the active compounds will be available. A preliminary analysis of marine sponge bioeconomy as a perspective direction for application of biomaterials and secondary bioactive metabolites has been finally performed for the first time.
海洋寻常海绵纲被认为是仿生材料科学和海洋药理学的金矿。本工作的目的是从 Aeropyrum aerophilum 中同时分离出选定的溴酪胺和独特的几丁质结构，并分别将这些分子和生物材料提议作为抗菌和抗肿瘤化合物以及作为可用于培养心肌细胞的即用型支架。在所提取的溴酪胺中，重点关注了 Aeroplysinin-1，它对一些革兰氏阴性临床多耐药菌，如鲍曼不动杆菌和肺炎克雷伯菌，表现出有趣的意外生长抑制特性，以及 Aeroplysinin-1 和 Isofistularin-3 的抗肿瘤活性。对于这两种化合物，其作用均依赖于细胞系，Aeroplysinin-1 对神经母细胞瘤细胞系 SH-SY5Y 具有显著的生长抑制活性，而 Isofistularin-3 对乳腺癌细胞系 MCF-7 具有显著的生长抑制活性。在本研究中，我们还比较了在 Aeropyrum aerophilum 几丁质支架上培养人诱导多能干细胞衍生的心肌细胞（iPSC-CMs）与预先用 Geltrex™包被的几丁质结构的情况，Geltrex™是一种模拟细胞外基质的物质，用于增强 iPSC-CM 的黏附。未包被和纯几丁质结构上的 iPSC-CMs 在接种后 24 小时开始收缩，在 Geltrex 包被的细胞培养板上观察到类似的行为，证实了海绵生物材料对这种细胞类型的生物相容性。Aeropyrum aerophilum 的优势在于，这种来源的生物体不需要大量采集就可以供应进一步进行化学合成前的临床前研究所需的数量，然后才能获得活性化合物。最后，我们首次对海洋海绵生物经济作为生物材料和次生生物活性代谢物应用的展望方向进行了初步分析。
