Fishing antioxidant 4-hydroxycoumarin derivatives: synthesis, characterization, and in vitro assessments.

In this work the antioxidant activity of eighteen 4-hydroxycoumarin coumarin derivatives was assessed, six of which are commercially available and the other twelve were synthesized and chemically characterized. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH• and ABTS•+) and a metal chelating activity assay. Six synthetic coumarins (4a, 4g, 4h, 4i, 4k, 4l) had a scavenging capacity of DPPH• higher than butylated hydroxytoluene (BHT)(IC50=0.58 mM) and compound 4a (4-hydroxy-6-methoxy-2H-chromen-2-one) with an IC50=0.05 mM outperformed both BHT and ascorbic acid (IC50=0.06mM). Nine hydroxycoumarins had a scavenging capacity against ABTS•+ greater (C3, 4a, 4c) or comparable (C1, C2, C4, C6, 4g, 4l) to Trolox (IC50=34.34µM). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (C2, C5, C6, 4a, 4b, 4h, 4i, 4j, 4k, 4l) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency.