Department of Chemistry, UiT The Arctic University of Norway, Breivika, N-9037 Tromsø, Norway.
Marbio, The Norwegian College of Fishery Science, UiT The Arctic University of Norway, Breivika, N-9037 Tromsø, Norway.
Bioorg Chem. 2019 Mar;84:106-114. doi: 10.1016/j.bioorg.2018.11.024. Epub 2018 Nov 22.
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.
海洋环境仍然是发现和开发新型生物活性化合物的丰富来源。本文描述了一种海洋 2,5-二酮哌嗪 barettin 的小分子杂环类似物文库的设计、合成和生物评价，barettin 是一种强大的天然抗氧化剂。通过主要关注溴化吲哚和 barettin 杂环核心的影响，合成了 19 个化合物。这些化合物包含一个杂环核心，要么是 2,5-二酮哌嗪，要么是咪唑烷二酮或噻唑烷二酮，主要用各种大体积取代基单取代。用 HepG2 细胞在细胞脂质过氧化测定中筛选了这些合成化合物的活性。一些合成化合物表现出比阳性对照 barettin 更好的抗氧化性能。两种制备的化合物显示出与商业抗氧化剂相似的抑制活性，在低 µg/mL 浓度下具有显著的抑制作用。还研究了化合物的毒性对 MRC-5 肺成纤维细胞的影响，在 50 µg/mL 浓度下，没有一种包含的化合物显示出任何毒性。
