Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin

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 mu g/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 mu g/mL.


2,5-Diketopiperazine, Barettin, Heterocycle, CLPAA, Structure-activity relationship, Marine natural products

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Supplementary Data 1. The 1H NMR and 13C NMR data of all evaluated compounds can be viewed in the online version of this article at the publisher’s web site.
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How to cite
Labriere Christophe, Andersen Jeanette H., Albrigtsen Marte, Hansen Jorn H., Svenson Johan (2019). Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin. Bioorganic Chemistry. 84. 106-114. https://doi.org/10.1016/j.bioorg.2018.11.024, https://archimer.ifremer.fr/doc/00605/71673/

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