Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin

Type Article
Date 2019-03
Language English
Author(s) Labriere Christophe1, 4, Andersen Jeanette H.2, Albrigtsen Marte2, Hansen Jorn H.1, Svenson Johan1, 3
Affiliation(s) 1 : UiT, Dept Chem, N-9037 Tromso, Norway.
2 : UiT, Norwegian Coll Fishery Sci, Marbio, N-9037 Tromso, Norway.
3 : RISE Res Inst Sweden, Dept Chem & Mat, Box 857, SE-50115 Boras, Sweden.
4 : Univ Bretagne Occidentale, Biodimar, LEMAR, UMR 6539, Rue Dumont dUrville, F-29280 Plouzane, France.
Source Bioorganic Chemistry (0045-2068) (Academic Press Inc Elsevier Science), 2019-03 , Vol. 84 , P. 106-114
DOI 10.1016/j.bioorg.2018.11.024
WOS© Times Cited 11
Keyword(s) 2,5-Diketopiperazine, Barettin, Heterocycle, CLPAA, Structure-activity relationship, Marine natural products

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.

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