Abstract
LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum "Sargassaceae" dereplicated eleven compounds 1-11. Further phytochemical investigation afforded two new aryl cresol 12-13, along with eight known compounds 14-21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes' active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.