New 5-LOX and 15-LOX Inhibitors Isolated from Red Sea Derived Brown Alga Sarragassum Cinnerum: An In Silico-Supported Study

Sargassum is a brown algal genus inhabiting tropical region. Metabolomic profiling of Sarragassum cinnerum “ 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, MCF7, and CACO2. Molecular targets of the bioactive compounds using a pharmacophore-based virtual screening, predicts 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The validation step revealed 12 and 13 inhibited 5-LOX more prudentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico analysis 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. Taken together, unique metabolites in S. cinnerum had potential anticancer activity supported with in-silico investigations to facility drug discovery and development processes.