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

Abstract

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae <i>Sargassum cinereum</i> "Sargassaceae" dereplicated eleven compounds <b>1</b>-<b>11</b>. Further phytochemical investigation afforded two new aryl cresol <b>12</b>-<b>13</b>, along with eight known compounds <b>14</b>-<b>21</b>. Both new metabolites, along with <b>19,</b> 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 <b>12</b> and <b>13</b> were able to inhibit 5-LOX more preferentially than 15-LOX, while <b>19</b> 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 <b>12</b> and <b>13</b> toward 5-LOX and 15-LOX.