Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

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.

Automated summary

LC-MS-assisted metabolomic profiling of Red Sea-derived brown algae Sargassum cinereum Sargassaceae identified eleven compounds, including two new aryl cresols and eight known compounds. These metabolites exhibited moderate in vitro antiproliferative activity against various cancer cell lines, potentially through inhibiting 5-LOX and 15-LOX. Further enzyme assays and in silico investigations provided insights into the mechanisms behind their inhibitory activity.