The development of alternative ecological and effective antifouling technologies is still challenging. Synthesis of nature-inspired compounds has been exploited, given the potential to assure commercial supplies of potential ecofriendly antifouling agents. In this direction, the antifouling activity of a series of nineteen synthetic small molecules, with chemical similarities with natural products, were exploited in this work. Six (4, 5, 7, 10, 15 and 17) of the tested xanthones showed in vivo activity toward the settlement of Mytilus galloprovincialis larvae (EC₅₀: 3.53–28.60 µM) and low toxicity to this macrofouling species (LC₅₀ > 500 µM and LC₅₀/EC₅₀: 17.42–141.64), and two of them (7 and 10) showed no general marine ecotoxicity (<10% of Artemia salina mortality) after 48 h of exposure. Regarding the mechanism of action in mussel larvae, the best performance compounds 4 and 5 might be acting by the inhibition of acetylcholinesterase activity (in vitro and in silico studies), while 7 and 10 showed specific targets (proteomic studies) directly related with the mussel adhesive structure (byssal threads), given by the alterations in the expression of Mytilus collagen proteins (PreCols) and proximal thread proteins (TMPs). A quantitative structure-activity relationship (QSAR) model was built with predictive capacity to enable speeding the design of new potential active compounds.

中文翻译：

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仿生（硫）氧杂蒽酮的结构-防污活性关系和分子靶标。


开发替代生态且有效的防污技术仍然具有挑战性。鉴于有可能确保潜在的生态友好型防污剂的商业供应，已经开发了受自然启发的化合物的合成。在这个方向上，这项工作开发了一系列十九种合成小分子的防污活性，这些小分子与天然产物具有化学相似性。六种（ 4 、 5 、 7 、 10 、 15和17 ）测试的氧杂蒽酮显示出体内对贻贝幼虫沉降的活性（EC ₅₀ ： 3.53–28.60 µM），并且对这种大型污垢物种具有低毒性（LC ₅₀ >） 500 µM 和 LC ₅₀ /EC ₅₀ ：17.42–141.64），其中两种（ 7和10 ）在暴露 48 小时后没有表现出一般海洋生态毒性（卤虫死亡率的 <10%）。关于贻贝幼虫的作用机制，性能最好的化合物4和5可能是通过抑制乙酰胆碱酯酶活性（体外和计算机研究）发挥作用，而7和10显示与贻贝直接相关的特定靶点（蛋白质组学研究）粘附结构（足丝），由贻贝胶原蛋白（PreCols）和近端丝蛋白（TMP）表达的改变而产生。建立了具有预测能力的定量构效关系（QSAR）模型，能够加快新的潜在活性化合物的设计。