Niemann Hendrik, Marmann Andreas, Lin Wenhan, Proksch Peter
Nat Prod Commun. 2015 Jan;10(1):219-31.
Sponge derived bromotyrosines are a multifaceted class of marine bioactive compounds that are important for the chemical defense of sponges but also for drug discovery programs as well as for technical applications in the field of antifouling constituents. These compounds, which are mainly accumulated by Verongid sponges, exhibit a diverse range of bioactivities including antibiotic, cytotoxic and antifouling effects. In spite of the simple biogenetic building blocks, which consist only of brominated tyrosine and tyramine units, an impressive diversity of different compounds is obtained through different linkages between these precursors and through structural modifications of the side chains and/or aromatic rings resembling strategies that are known from combinatorial chemistry. As examples for bioactive, structurally divergent bromotyrosines psammaplin A, Aplysina alkaloids featuring aerothionin, aeroplysinin-1 and the dienone, and the bastadins, including the synthetically derived hemibastadin congeners, have been selected for this review. Whereas all of these natural products are believed to be involved in the chemical defense of sponges, some of them may also be of particular relevance to drug discovery due to their interaction with specific molecular targets in eukaryotic cells. These targets involve important enzymes and receptors, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), which are inhibited by psammaplin A, as well as ryanodine receptors that are targeted by bastadine type compounds. The hemibastadins such as the synthetically derived dibromohemibastadin are of particular interest due to their antifouling activity. For the latter, a phenoloxidase which catalyzes the bioglue formation needed for firm attachment of fouling organisms to a given substrate was identified as a molecular target. The Aplysina alkaloids finally provide a vivid example for dynamic wound induced bioconversions of natural products that generate highly efficient chemical weapons precisely when and where needed.
海绵来源的溴酪氨酸是一类具有多方面特性的海洋生物活性化合物，它们对海绵的化学防御至关重要，在药物研发项目以及防污成分领域的技术应用中也具有重要意义。这些化合物主要由Verongid海绵积累，具有多种生物活性，包括抗生素、细胞毒性和防污作用。尽管其生物合成的基本构建单元很简单，仅由溴化酪氨酸和酪胺单元组成，但通过这些前体之间不同的连接方式以及侧链和/或芳香环的结构修饰，能得到令人印象深刻的不同化合物多样性，这类似于组合化学中已知的策略。作为具有生物活性、结构不同的溴酪氨酸的例子，本综述选择了沙马普林A、具有气硫素、气多赖氨酸-1和二烯酮的Aplysina生物碱以及包括合成衍生的半bastadin同系物在内的bastadin。虽然所有这些天然产物都被认为参与了海绵的化学防御，但其中一些由于与真核细胞中的特定分子靶点相互作用，可能对药物研发也具有特殊意义。这些靶点包括重要的酶和受体，如被沙马普林A抑制的组蛋白脱乙酰酶（HDAC）和DNA甲基转移酶（DNMT），以及被bastadin类化合物靶向的兰尼碱受体。合成衍生的二溴半bastadin等半bastadin因其防污活性而特别受关注。对于后者，一种催化污垢生物牢固附着在给定底物上所需生物胶水形成的酚氧化酶被确定为分子靶点。Aplysina生物碱最终为天然产物在动态伤口诱导下的生物转化提供了一个生动的例子，这些转化能在需要的时间和地点精确地产生高效的化学武器。
