Synthesis and biological evaluation of (2,5-dihydro-1H-pyrrol-1-yl)-2H-chromen-2-ones as free radical scavengers

The allylation of aminocoumarins in the presence of excess of anhydrous K2CO3 and allyl bromide to diallylaminocoumarins is described. The Ring Closing Metathesis reaction of the later with the Grubbs’ 1rst generation catalyst under reflux or MW irradiation has resulted mainly to (2,5-dihydro-1H-pyrrol-1-yl)coumarins and (1H-pyrrol-1-yl)coumarins. The new compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase LO and (v) to scavenge hydroxyl radicals. Most of them were found to be potent lipid peroxidation inhibitors in vitro. The majority of the compounds showed significant hydroxyl radical scavenging activity. Compounds 11a and 12c presenting higher LO inhibitory activity as well as compound 17 were found to present a promising antioxidant and LO inhibitory profile.

Graphical abstractThe synthesized compounds act as free radical scavengersFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► (2,5-Dihydro-1H-pyrrol-1-yl)-, (1H-pyrrol-1-yl)coumarins from diallylaminocoumarins. ► Most of them were found to be potent lipid peroxidation inhibitors in vitro. ► Those compounds show significant hydroxyl radical scavenging activity. ► Compounds 11a and 12c present higher LO inhibitory activity. ► Compound 17 present a promising antioxidant and LO inhibitory profile.