The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL.

中文翻译：

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杂环细胞脂质过氧化抑制剂受海洋抗氧化剂Barettin的启发。

海洋环境仍然是发现和开发新型生物活性化合物的丰富资源。本文描述了海洋2,5-二酮哌嗪巴雷汀（一种强大的天然抗氧化剂）的小分子杂环模拟物的文库的设计，合成和生物学评估。通过主要关注来自Barettin的溴化吲哚和杂环核心的影响，制备了19种化合物的文库。所述化合物包含杂环核，其为2，5-二酮哌嗪，咪唑烷二酮或噻吩并噻唑烷酮，其主要被范围广泛的取代基单取代。使用HepG2细胞在细胞脂质过氧化测定中筛选制备的化合物的活性。几种合成化合物显示出优于阳性对照巴雷菌素的抗氧化性能。所制备的两种化合物显示出与市售抗氧化剂相似的抑制活性，在低µg / mL浓度下具有明显的抑制作用。还研究了该化合物对MRC-5肺成纤维细胞的毒性，所含化合物均未显示50 µg / mL的毒性。